Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

Almendro, Vanessa; Cheng, Yu -Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege  G.; Helland, Åslaug; Rye, Inga  H.; Borresen-Dale, Anne -Lise; Maruyama, Reo; van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin  L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

doi:10.1016/j.celrep.2013.12.041

Title: Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

Abstract

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.

Authors:

Almendro, Vanessa ^[1]; Cheng, Yu -Kang ^[2]; Randles, Amanda ^[3]; Itzkovitz, Shalev ^[4]; Marusyk, Andriy ^[5]; Ametller, Elisabet ^[6]; Gonzalez-Farre, Xavier ^[6]; Muñoz, Montse ^[6]; Russnes, Hege G. ^[7]; Helland, Åslaug ^[8]; Rye, Inga H. ^[9]; Borresen-Dale, Anne -Lise ^[9]; Maruyama, Reo ^[5]; van Oudenaarden, Alexander ^[10]; Dowsett, Mitchell ^[11]; Jones, Robin L. ^[12]; Reis-Filho, Jorge ^[13]; Gascon, Pere ^[6]; Gönen, Mithat ^[14]; Michor, Franziska ^[2] more »

Dana-Farber Cancer Institute, Boston, MA (United States); Brigham and Women's Hospital, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Institut d'Investigacions Biomediques, Barcelona (Spain)
Dana-Farber Cancer Institute, Boston, MA (United States); Harvard School of Public Health, Boston, MA (United States)
Dana-Farber Cancer Institute, Boston, MA (United States); Harvard School of Public Health, Boston, MA (United States); Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
MIT (Massachusetts Inst. of Technology), Cambridge, MA (United States); Weizmann Institute of Science, Rehovot (Israel)
Dana-Farber Cancer Institute, Boston, MA (United States); Brigham and Women's Hospital, Boston, MA (United States); Harvard Medical School, Boston, MA (United States)
Institut d'Investigacions Biomediques, Barcelona (Spain)
Oslo Univ. Hospital Radiumhospitalet, Oslo (Norway); Univ. of Oslo, Oslo (Norway); Oslo Univ. Hospital, Oslo (Norway)
Oslo Univ. Hospital Radiumhospitalet, Oslo (Norway); Oslo Univ. Hospital, Oslo (Norway); Univ. of Oslo, Oslo (Norway)
Oslo Univ. Hospital Radiumhospitalet, Oslo (Norway); Univ. of Oslo, Oslo (Norway)
MIT (Massachusetts Inst. of Technology), Cambridge, MA (United States); Royal Netherlands Academy of Arts and Sciences and Univ. Medical Center Utrecht, Utrecht (The Netherlands)
The Royal Marsden Hospital, London (United Kingdom)
The Royal Marsden Hospital, London (United Kingdom); Seattle Cancer Care Alliance, Seattle, WA (United States)
The Royal Marsden Hospital, London (United Kingdom); Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
Memorial Sloan-Kettering Cancer Center, New York, NY (United States)
Dana-Farber Cancer Institute, Boston, MA (United States); Brigham and Women's Hospital, Boston, MA (United States); Harvard Medical School, Boston, MA (United States); Harvard Stem Cell Institute, Cambridge, MA (United States); Broad Institute, Cambridge, MA (United States)

Publication Date:: Sat Feb 01 00:00:00 EST 2014

Research Org.:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1201672

Resource Type:: Journal Article: Accepted Manuscript

Journal Name:: Cell Reports

Additional Journal Information:: Journal Volume: 6; Journal Issue: 3; Journal ID: ISSN 2211-1247

Publisher:: Elsevier

Country of Publication:: United States

Language:: English

Subject:: 62 RADIOLOGY AND NUCLEAR MEDICINE

Citation Formats


                    Almendro, Vanessa, Cheng, Yu -Kang, Randles, Amanda, Itzkovitz, Shalev, Marusyk, Andriy, Ametller, Elisabet, Gonzalez-Farre, Xavier, Muñoz, Montse, Russnes, Hege  G., Helland, Åslaug, Rye, Inga  H., Borresen-Dale, Anne -Lise, Maruyama, Reo, van Oudenaarden, Alexander, Dowsett, Mitchell, Jones, Robin  L., Reis-Filho, Jorge, Gascon, Pere, Gönen, Mithat, Michor, Franziska, and Polyak, Kornelia. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity.  United States: N. p., 2014. 
        Web.  doi:10.1016/j.celrep.2013.12.041.

Copy to clipboard


                    Almendro, Vanessa, Cheng, Yu -Kang, Randles, Amanda, Itzkovitz, Shalev, Marusyk, Andriy, Ametller, Elisabet, Gonzalez-Farre, Xavier, Muñoz, Montse, Russnes, Hege  G., Helland, Åslaug, Rye, Inga  H., Borresen-Dale, Anne -Lise, Maruyama, Reo, van Oudenaarden, Alexander, Dowsett, Mitchell, Jones, Robin  L., Reis-Filho, Jorge, Gascon, Pere, Gönen, Mithat, Michor, Franziska, & Polyak, Kornelia. Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity.  United States.  https://doi.org/10.1016/j.celrep.2013.12.041

Copy to clipboard


                    Almendro, Vanessa, Cheng, Yu -Kang, Randles, Amanda, Itzkovitz, Shalev, Marusyk, Andriy, Ametller, Elisabet, Gonzalez-Farre, Xavier, Muñoz, Montse, Russnes, Hege  G., Helland, Åslaug, Rye, Inga  H., Borresen-Dale, Anne -Lise, Maruyama, Reo, van Oudenaarden, Alexander, Dowsett, Mitchell, Jones, Robin  L., Reis-Filho, Jorge, Gascon, Pere, Gönen, Mithat, Michor, Franziska, and Polyak, Kornelia. 2014.  
        "Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity".  United States.  https://doi.org/10.1016/j.celrep.2013.12.041.  https://www.osti.gov/servlets/purl/1201672.

Copy to clipboard


                    
@article{osti_1201672,

  title        = {Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity},

  author       = {Almendro, Vanessa and Cheng, Yu -Kang and Randles, Amanda and Itzkovitz, Shalev and Marusyk, Andriy and Ametller, Elisabet and Gonzalez-Farre, Xavier and Muñoz, Montse and Russnes, Hege  G. and Helland, Åslaug and Rye, Inga  H. and Borresen-Dale, Anne -Lise and Maruyama, Reo and van Oudenaarden, Alexander and Dowsett, Mitchell and Jones, Robin  L. and Reis-Filho, Jorge and Gascon, Pere and Gönen, Mithat and Michor, Franziska and Polyak, Kornelia},

  abstractNote = {Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.},

  doi          = {10.1016/j.celrep.2013.12.041},

  url          = {https://www.osti.gov/biblio/1201672},
  journal      = {Cell Reports},

  issn         = {2211-1247},

  number       = 3,

  volume       = 6,

  place        = {United States},

  year         = {Sat Feb 01 00:00:00 EST 2014},

  month        = {Sat Feb 01 00:00:00 EST 2014}

}

Copy to clipboard

Journal Article:

Free Publicly Available Full Text

Accepted Manuscript (DOE)

Publisher's Version of Record

https://doi.org/10.1016/j.celrep.2013.12.041

Other availability

Search WorldCat to find libraries that may hold this journal

Citation Metrics:

Cited by: 192 works

Citation information provided by
Web of Science

Save / Share:

Export Metadata

Save to My Library

Works referenced in this record:

Prospective identification of tumorigenic breast cancer cells
journal, March 2003

Al-Hajj, M.; Wicha, M. S.; Benito-Hernandez, A.
Proceedings of the National Academy of Sciences, Vol. 100, Issue 7
https://doi.org/10.1073/pnas.0530291100

Cellular Heterogeneity and Molecular Evolution in Cancer
journal, January 2013

Almendro, Vanessa; Marusyk, Andriy; Polyak, Kornelia
Annual Review of Pathology: Mechanisms of Disease, Vol. 8, Issue 1
https://doi.org/10.1146/annurev-pathol-020712-163923

Cell type-specific DNA methylation patterns in the human breast
journal, September 2008

Bloushtain-Qimron, N.; Yao, J.; Snyder, E. L.
Proceedings of the National Academy of Sciences, Vol. 105, Issue 37
https://doi.org/10.1073/pnas.0805206105

Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
journal, June 2006

Burcombe, Russell; Wilson, George D.; Dowsett, Mitch
Breast Cancer Research, Vol. 8, Issue 3
https://doi.org/10.1186/bcr1508

Epithelial-mesenchymal transition, cancer stem cells and treatment resistance
journal, January 2012

Dave, Bhuvanesh; Mittal, Vivek; Tan, Nicholas M.
Breast Cancer Research, Vol. 14, Issue 1
https://doi.org/10.1186/bcr2938

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
journal, January 2012

Ding, Li; Ley, Timothy J.; Larson, David E.
Nature, Vol. 481, Issue 7382
https://doi.org/10.1038/nature10738

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
journal, May 2007

Engelman, J. A.; Zejnullahu, K.; Mitsudomi, T.
Science, Vol. 316, Issue 5827
https://doi.org/10.1126/science.1141478

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657
journal, September 2012

Esserman, Laura J.; Berry, Donald A.; DeMichele, Angela
Journal of Clinical Oncology, Vol. 30, Issue 26
https://doi.org/10.1200/JCO.2011.39.2779

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
journal, March 2012

Gerlinger, Marco; Rowan, Andrew J.; Horswell, Stuart
New England Journal of Medicine, Vol. 366, Issue 10
https://doi.org/10.1056/NEJMoa1113205

Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas
journal, April 2010

Geyer, Felipe C.; Weigelt, Britta; Natrajan, Rachael
The Journal of Pathology, Vol. 220, Issue 5
https://doi.org/10.1002/path.2675

Tumor heterogeneity: biological implications and therapeutic consequences
journal, January 1983

Heppner, Gloria H.; Miller, Bonnie E.
CANCER AND METASTASIS REVIEW, Vol. 2, Issue 1
https://doi.org/10.1007/BF00046903

Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection
journal, March 2012

Hernandez, Lucia; Wilkerson, Paul M.; Lambros, Maryou B.
The Journal of Pathology, Vol. 227, Issue 1
https://doi.org/10.1002/path.3990

Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer
journal, September 2006

Hess, Kenneth R.; Anderson, Keith; Symmans, W. Fraser
Journal of Clinical Oncology, Vol. 24, Issue 26
https://doi.org/10.1200/JCO.2006.05.6861

The CD44+/CD24-phenotype is enriched in basal-like breast tumors
journal, June 2008

Honeth, Gabriella; Bendahl, Pär-Ola; Ringnér, Markus
Breast Cancer Research, Vol. 10, Issue 3
https://doi.org/10.1186/bcr2108

Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy
journal, December 2012

Houssami, Nehmat; Macaskill, Petra; von Minckwitz, Gunter
European Journal of Cancer, Vol. 48, Issue 18
https://doi.org/10.1016/j.ejca.2012.05.023

Intravital imaging of metastatic behavior through a mammary imaging window
journal, November 2008

Kedrin, Dmitriy; Gligorijevic, Bojana; Wyckoff, Jeffrey
Nature Methods, Vol. 5, Issue 12
https://doi.org/10.1038/nmeth.1269

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
journal, May 2011

Lee, H. E.; Kim, J. H.; Kim, Y. J.
British Journal of Cancer, Vol. 104, Issue 11
https://doi.org/10.1038/bjc.2011.159

Intrinsic Resistance of Tumorigenic Breast Cancer Cells to Chemotherapy
journal, April 2008

Li, X.; Lewis, M. T.; Huang, J.
JNCI Journal of the National Cancer Institute, Vol. 100, Issue 9
https://doi.org/10.1093/jnci/djn123

The Prognostic Role of a Gene Signature from Tumorigenic Breast-Cancer Cells
journal, January 2007

Liu, Rui; Wang, Xinhao; Chen, Grace Y.
New England Journal of Medicine, Vol. 356, Issue 3
https://doi.org/10.1056/NEJMoa063994

Genetic clonal diversity predicts progression to esophageal adenocarcinoma
journal, March 2006

Maley, Carlo C.; Galipeau, Patricia C.; Finley, Jennifer C.
Nature Genetics, Vol. 38, Issue 4
https://doi.org/10.1038/ng1768

Intra-tumour heterogeneity: a looking glass for cancer?
journal, April 2012

Marusyk, Andriy; Almendro, Vanessa; Polyak, Kornelia
Nature Reviews Cancer, Vol. 12, Issue 5
https://doi.org/10.1038/nrc3261

Different prognostic significance of Ki-67 change between pre- and post-neoadjuvant chemotherapy in various subtypes of breast cancer
journal, November 2012

Matsubara, Nobuaki; Mukai, Hirofumi; Fujii, Satoshi
Breast Cancer Research and Treatment, Vol. 137, Issue 1
https://doi.org/10.1007/s10549-012-2344-6

Cancer as an evolutionary and ecological process
journal, November 2006

Merlo, Lauren M. F.; Pepper, John W.; Reid, Brian J.
Nature Reviews Cancer, Vol. 6, Issue 12
https://doi.org/10.1038/nrc2013

A Comprehensive Survey of Clonal Diversity Measures in Barrett's Esophagus as Biomarkers of Progression to Esophageal Adenocarcinoma
journal, October 2010

Merlo, Lauren M. F.; Shah, Najaf A.; Li, Xiaohong
Cancer Prevention Research, Vol. 3, Issue 11
https://doi.org/10.1158/1940-6207.CAPR-10-0108

High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma: Genetic Heterogeneity and HNSCC Outcome
journal, May 2013

Mroz, Edmund A.; Tward, Aaron D.; Pickering, Curtis R.
Cancer, Vol. 119, Issue 16
https://doi.org/10.1002/cncr.28150

Tumour evolution inferred by single-cell sequencing
journal, March 2011

Navin, Nicholas; Kendall, Jude; Troge, Jennifer
Nature, Vol. 472, Issue 7341
https://doi.org/10.1038/nature09807

Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
journal, November 2010

Nazarian, Ramin; Shi, Hubing; Wang, Qi
Nature, Vol. 468, Issue 7326
https://doi.org/10.1038/nature09626

Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype
journal, February 2010

Park, So Yeon; Gönen, Mithat; Kim, Hee Jung
Journal of Clinical Investigation, Vol. 120, Issue 2
https://doi.org/10.1172/JCI40724

Heterogeneity for Stem Cell-Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer
journal, January 2010

Park, S. Y.; Lee, H. E.; Li, H.
Clinical Cancer Research, Vol. 16, Issue 3
https://doi.org/10.1158/1078-0432.CCR-09-1532

Molecular portraits of human breast tumours
journal, August 2000

Perou, Charles M.; Sørlie, Therese; Eisen, Michael B.
Nature, Vol. 406, Issue 6797
https://doi.org/10.1038/35021093

Heterogeneity in breast cancer
journal, October 2011

Polyak, Kornelia
Journal of Clinical Investigation, Vol. 121, Issue 10
https://doi.org/10.1172/JCI60534

Overcoming Intrinsic Multidrug Resistance in Melanoma by Blocking the Mitochondrial Respiratory Chain of Slow-Cycling JARID1Bhigh Cells
journal, June 2013

Roesch, Alexander; Vultur, Adina; Bogeski, Ivan
Cancer Cell, Vol. 23, Issue 6
https://doi.org/10.1016/j.ccr.2013.05.003

Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
journal, February 2008

Sakai, Wataru; Swisher, Elizabeth M.; Karlan, Beth Y.
Nature, Vol. 451, Issue 7182
https://doi.org/10.1038/nature06633

The cell kinetics of human mammary cancers
journal, May 1979

Schiffer, L. M.; Braunschweiger, P. G.; Stragand, J. J.
Cancer, Vol. 43, Issue 5
https://doi.org/10.1002/1097-0142(197905)43:5<1707::AID-CNCR2820430522>3.0.CO;2-A

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
journal, April 2010

Sharma, Sreenath V.; Lee, Diana Y.; Li, Bihua
Cell, Vol. 141, Issue 1
https://doi.org/10.1016/j.cell.2010.02.027

Molecular Definition of Breast Tumor Heterogeneity
journal, March 2007

Shipitsin, Michail; Campbell, Lauren L.; Argani, Pedram
Cancer Cell, Vol. 11, Issue 3
https://doi.org/10.1016/j.ccr.2007.01.013

Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer
journal, March 2010

Silver, Daniel P.; Richardson, Andrea L.; Eklund, Aron C.
Journal of Clinical Oncology, Vol. 28, Issue 7
https://doi.org/10.1200/JCO.2009.22.4725

The landscape of cancer genes and mutational processes in breast cancer
journal, May 2012

Stephens, Philip J.; Tarpey, Patrick S.; Davies, Helen
Nature, Vol. 486, Issue 7403
https://doi.org/10.1038/nature11017

Genetic heterogeneity and cancer drug resistance
journal, April 2012

Turner, Nicholas C.; Reis-Filho, Jorge S.
The Lancet Oncology, Vol. 13, Issue 4
https://doi.org/10.1016/S1470-2045(11)70335-7

Intratumor Heterogeneity: Seeing the Wood for the Trees
journal, March 2012

Yap, T. A.; Gerlinger, M.; Futreal, P. A.
Science Translational Medicine, Vol. 4, Issue 127
https://doi.org/10.1126/scitranslmed.3003854

Overcoming Intrinsic Multidrug Resistance in Melanoma by Blocking the Mitochondrial Respiratory Chain of Slow-Cycling JARID1Bhigh Cells
journal, June 2013

Roesch, Alexander; Vultur, Adina; Bogeski, Ivan
Cancer Cell, Vol. 23, Issue 6
https://doi.org/10.1016/j.ccr.2013.05.003

Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy
journal, December 2012

Houssami, Nehmat; Macaskill, Petra; von Minckwitz, Gunter
European Journal of Cancer, Vol. 48, Issue 18
https://doi.org/10.1016/j.ejca.2012.05.023

Primary chemotherapy in locally advanced breast cancer (LABC): effects on tumour proliferative activity, bcl-2 expression and the relationship between tumour regression and biological markers
journal, October 1998

Collecchi, P.; Baldini, E.; Giannessi, P.
European Journal of Cancer, Vol. 34, Issue 11
https://doi.org/10.1016/s0959-8049(98)00213-5

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
journal, May 2011

Lee, H. E.; Kim, J. H.; Kim, Y. J.
British Journal of Cancer, Vol. 104, Issue 11
https://doi.org/10.1038/bjc.2011.159

Intravital imaging of metastatic behavior through a mammary imaging window
journal, November 2008

Kedrin, Dmitriy; Gligorijevic, Bojana; Wyckoff, Jeffrey
Nature Methods, Vol. 5, Issue 12
https://doi.org/10.1038/nmeth.1269

Intra-tumour heterogeneity: a looking glass for cancer?
journal, April 2012

Marusyk, Andriy; Almendro, Vanessa; Polyak, Kornelia
Nature Reviews Cancer, Vol. 12, Issue 5
https://doi.org/10.1038/nrc3261

Cell type-specific DNA methylation patterns in the human breast
journal, September 2008

Bloushtain-Qimron, N.; Yao, J.; Snyder, E. L.
Proceedings of the National Academy of Sciences, Vol. 105, Issue 37
https://doi.org/10.1073/pnas.0805206105

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
journal, May 2007

Engelman, J. A.; Zejnullahu, K.; Mitsudomi, T.
Science, Vol. 316, Issue 5827
https://doi.org/10.1126/science.1141478

Cellular Heterogeneity and Molecular Evolution in Cancer
journal, January 2013

Almendro, Vanessa; Marusyk, Andriy; Polyak, Kornelia
Annual Review of Pathology: Mechanisms of Disease, Vol. 8, Issue 1
https://doi.org/10.1146/annurev-pathol-020712-163923

Genome-Wide Functional Synergy between Amplified and Mutated Genes in Human Breast Cancer
journal, November 2008

Nikolsky, Yuri; Sviridov, Evgeny; Yao, Jun
Cancer Research, Vol. 68, Issue 22
https://doi.org/10.1158/0008-5472.can-08-3082

Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
journal, June 2006

Burcombe, Russell; Wilson, George D.; Dowsett, Mitch
Breast Cancer Research, Vol. 8, Issue 3
https://doi.org/10.1186/bcr1508

The CD44+/CD24-phenotype is enriched in basal-like breast tumors
journal, June 2008

Honeth, Gabriella; Bendahl, Pär-Ola; Ringnér, Markus
Breast Cancer Research, Vol. 10, Issue 3
https://doi.org/10.1186/bcr2108

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.
journal, August 1998

Fisher, B.; Bryant, J.; Wolmark, N.
Journal of Clinical Oncology, Vol. 16, Issue 8
https://doi.org/10.1200/jco.1998.16.8.2672

Recommendations From an International Expert Panel on the Use of Neoadjuvant (Primary) Systemic Treatment of Operable Breast Cancer: An Update
journal, April 2006

Kaufmann, Manfred; Hortobagyi, Gabriel N.; Goldhirsch, Aron
Journal of Clinical Oncology, Vol. 24, Issue 12
https://doi.org/10.1200/jco.2005.02.6187

Works referencing / citing this record:

Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity
journal, February 2017

Turner, Kristen M.; Deshpande, Viraj; Beyter, Doruk
Nature, Vol. 543, Issue 7643
https://doi.org/10.1038/nature21356

Subclonal diversification of primary breast cancer revealed by multiregion sequencing
journal, June 2015

Yates, Lucy R.; Gerstung, Moritz; Knappskog, Stian
Nature Medicine, Vol. 21, Issue 7
https://doi.org/10.1038/nm.3886

Computational Cancer Biology: An Evolutionary Perspective
journal, February 2016

Beerenwinkel, Niko; Greenman, Chris D.; Lagergren, Jens
PLOS Computational Biology, Vol. 12, Issue 2
https://doi.org/10.1371/journal.pcbi.1004717

Punctuated copy number evolution and clonal stasis in triple-negative breast cancer
journal, August 2016

Gao, Ruli; Davis, Alexander; McDonald, Thomas O.
Nature Genetics, Vol. 48, Issue 10
https://doi.org/10.1038/ng.3641

Tumorigenesis: it takes a village
journal, July 2015

Tabassum, Doris P.; Polyak, Kornelia
Nature Reviews Cancer, Vol. 15, Issue 8
https://doi.org/10.1038/nrc3971

The shock of being united and symphiliosis: Another lesson from plants?
journal, July 2014

Lazebnik, Yuri
Cell Cycle, Vol. 13, Issue 15
https://doi.org/10.4161/cc.29704

Tunneling nanotubes: A bridge for heterogeneity in glioblastoma and a new therapeutic target?
journal, May 2019

Venkatesh, Varun Subramaniam; Lou, Emil
CANCER REPORTS, Vol. 2, Issue 6
https://doi.org/10.1002/cnr2.1185

Tumour heterogeneity and the evolution of polyclonal drug resistance
journal, July 2014

Burrell, Rebecca A.; Swanton, Charles
Molecular Oncology, Vol. 8, Issue 6
https://doi.org/10.1016/j.molonc.2014.06.005

Reconstructing cancer karyotypes from short read data: the half empty and half full glass
journal, November 2017

Eitan, Rami; Shamir, Ron
BMC Bioinformatics, Vol. 18, Issue 1
https://doi.org/10.1186/s12859-017-1929-9

The biology of circulating tumor cells
journal, June 2015

Pantel, K.; Speicher, M. R.
Oncogene, Vol. 35, Issue 10
https://doi.org/10.1038/onc.2015.192

Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer
journal, September 2018

Risom, Tyler; Langer, Ellen M.; Chapman, Margaret P.
Nature Communications, Vol. 9, Issue 1
https://doi.org/10.1038/s41467-018-05729-w

The impact of pharmacokinetic gene profiles across human cancers
journal, May 2018

Zimmermann, Michael T.; Therneau, Terry M.; Kocher, Jean-Pierre A.
BMC Cancer, Vol. 18, Issue 1
https://doi.org/10.1186/s12885-018-4345-2

Quantitative Spatial Analysis of Metabolic Heterogeneity Across in vivo and in vitro Tumor Models
journal, November 2019

Heaster, Tiffany M.; Landman, Bennett A.; Skala, Melissa C.
Frontiers in Oncology, Vol. 9
https://doi.org/10.3389/fonc.2019.01144

Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression
journal, January 2018

Márquez-Jurado, Silvia; Díaz-Colunga, Juan; das Neves, Ricardo Pires
Nature Communications, Vol. 9, Issue 1
https://doi.org/10.1038/s41467-017-02787-4

Cancer-associated fibroblast compositions change with breast-cancer progression linking S100A4 and PDPN ratios with clinical outcome
posted_content, January 2020

Friedman, Gil; Levi-Galibov, Oshrat; David, Eyal
Nature Cancer
https://doi.org/10.1101/2020.01.12.903039

An analysis of genetic heterogeneity in untreated cancers
journal, August 2019

Reiter, Johannes G.; Baretti, Marina; Gerold, Jeffrey M.
Nature Reviews Cancer, Vol. 19, Issue 11
https://doi.org/10.1038/s41568-019-0185-x

Intra-tumor heterogeneity from a cancer stem cell perspective
journal, February 2017

Prasetyanti, Pramudita R.; Medema, Jan Paul
Molecular Cancer, Vol. 16, Issue 1
https://doi.org/10.1186/s12943-017-0600-4

Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine
journal, December 2016

Contreras, Alejandra V.; Cocom-Chan, Benjamin; Hernandez-Montes, Georgina
Frontiers in Physiology, Vol. 7
https://doi.org/10.3389/fphys.2016.00606

Initiation of aberrant DNA methylation patterns and heterogeneity in precancerous lesions of human hepatocellular cancer
journal, January 2017

Hlady, Ryan A.; Zhou, Dan; Puszyk, William
Epigenetics, Vol. 12, Issue 3
https://doi.org/10.1080/15592294.2016.1277297

Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state
journal, April 2019

Echeverria, Gloria V.; Ge, Zhongqi; Seth, Sahil
Science Translational Medicine, Vol. 11, Issue 488
https://doi.org/10.1126/scitranslmed.aav0936

Identification of neutral tumor evolution across cancer types
journal, January 2016

Williams, Marc J.; Werner, Benjamin; Barnes, Chris P.
Nature Genetics, Vol. 48, Issue 3
https://doi.org/10.1038/ng.3489

Understanding tumor ecosystems by single-cell sequencing: promises and limitations
journal, December 2018

Ren, Xianwen; Kang, Boxi; Zhang, Zemin
Genome Biology, Vol. 19, Issue 1
https://doi.org/10.1186/s13059-018-1593-z

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy
journal, April 2016

Findlay, John M.; Castro-Giner, Francesc; Makino, Seiko
Nature Communications, Vol. 7, Issue 1
https://doi.org/10.1038/ncomms11111

Clinical implications of changes in the diversity of c-MYC copy number variation after neoadjuvant chemotherapy in breast cancer
journal, November 2018

Chung, Yul Ri; Kim, Hyun Jeong; Kim, Milim
Scientific Reports, Vol. 8, Issue 1
https://doi.org/10.1038/s41598-018-35072-5

Interrogating open issues in cancer precision medicine with patient-derived xenografts
journal, January 2017

Byrne, Annette T.; Alférez, Denis G.; Amant, Frédéric
Nature Reviews Cancer, Vol. 17, Issue 4
https://doi.org/10.1038/nrc.2016.140

Breast Cancer Heterogeneity: Roles in Tumorigenesis and Therapeutic Implications
journal, February 2017

Pareja, Fresia; Marchiò, Caterina; Geyer, Felipe C.
Current Breast Cancer Reports, Vol. 9, Issue 1
https://doi.org/10.1007/s12609-017-0233-z

Caveolin-1 mediates chemoresistance in breast cancer stem cells via β-catenin/ABCG2 signaling pathway
journal, August 2014

Wang, Zhiyu; Wang, Neng; Li, Wenping
Carcinogenesis, Vol. 35, Issue 10
https://doi.org/10.1093/carcin/bgu155

Genetic traits for hematogeneous tumor cell dissemination in cancer patients
journal, March 2016

Joosse, Simon A.; Pantel, Klaus
Cancer and Metastasis Reviews, Vol. 35, Issue 1
https://doi.org/10.1007/s10555-016-9611-7

Classical pathology and mutational load of breast cancer - integration of two worlds: Phenotype-genotype correlations in breast cancer
journal, July 2015

Budczies, Jan; Bockmayr, Michael; Denkert, Carsten
The Journal of Pathology: Clinical Research, Vol. 1, Issue 4
https://doi.org/10.1002/cjp2.25

LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells
journal, August 2019

Cebrià-Costa, J. P.; Pascual-Reguant, L.; Gonzalez-Perez, A.
Oncogene, Vol. 39, Issue 1
https://doi.org/10.1038/s41388-019-0969-1

Evolutionary mechanism unifies the hallmarks of cancer: Hallmarks of cancer
journal, June 2014

Horne, Steven D.; Pollick, Sarah A.; Heng, Henry H. Q.
International Journal of Cancer, Vol. 136, Issue 9
https://doi.org/10.1002/ijc.29031

Breast cancer intra-tumor heterogeneity
journal, May 2014

Martelotto, Luciano G.; Ng, Charlotte KY; Piscuoglio, Salvatore
Breast Cancer Research, Vol. 16, Issue 3
https://doi.org/10.1186/bcr3658

An Emerging Allee Effect Is Critical for Tumor Initiation and Persistence
journal, September 2015

Böttger, Katrin; Hatzikirou, Haralambos; Voss-Böhme, Anja
PLOS Computational Biology, Vol. 11, Issue 9
https://doi.org/10.1371/journal.pcbi.1004366

A Big Bang model of human colorectal tumor growth
journal, February 2015

Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng
Nature Genetics, Vol. 47, Issue 3
https://doi.org/10.1038/ng.3214

Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer
journal, March 2016

Andrade, Sheila Siqueira; Gouvea, Iuri Estrada; Silva, Mariana Cristina C.
BMC Cancer, Vol. 16, Issue 1
https://doi.org/10.1186/s12885-016-2203-7

Cancer genomics: one cell at a time
journal, August 2014

Navin, Nicholas E.
Genome Biology, Vol. 15, Issue 8
https://doi.org/10.1186/s13059-014-0452-9

Intra-tumor heterogeneity of cancer cells and its implications for cancer treatment
journal, September 2015

Sun, Xiao-xiao; Yu, Qiang
Acta Pharmacologica Sinica, Vol. 36, Issue 10
https://doi.org/10.1038/aps.2015.92

Pan-cancer analysis of the extent and consequences of intratumor heterogeneity
journal, November 2015

Andor, Noemi; Graham, Trevor A.; Jansen, Marnix
Nature Medicine, Vol. 22, Issue 1
https://doi.org/10.1038/nm.3984

Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish
journal, January 2016

Tang, Qin; Moore, John C.; Ignatius, Myron S.
Nature Communications, Vol. 7, Issue 1
https://doi.org/10.1038/ncomms10358

Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights
journal, November 2016

Alfonso, J. C. L.; Köhn-Luque, A.; Stylianopoulos, T.
Scientific Reports, Vol. 6, Issue 1
https://doi.org/10.1038/srep37283

Stability-driven nonnegative matrix factorization to interpret spatial gene expression and build local gene networks
journal, April 2016

Wu, Siqi; Joseph, Antony; Hammonds, Ann S.
Proceedings of the National Academy of Sciences, Vol. 113, Issue 16
https://doi.org/10.1073/pnas.1521171113

Cancer Evolution: Mathematical Models and Computational Inference
journal, October 2014

Beerenwinkel, Niko; Schwarz, Roland F.; Gerstung, Moritz
Systematic Biology, Vol. 64, Issue 1
https://doi.org/10.1093/sysbio/syu081

Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer
journal, May 2018

Stover, Daniel G.; Gil Del Alcazar, Carlos R.; Brock, Jane
npj Breast Cancer, Vol. 4, Issue 1
https://doi.org/10.1038/s41523-018-0060-z

Applying evolutionary biology to address global challenges
journal, September 2014

Carroll, S. P.; Jorgensen, P. S.; Kinnison, M. T.
Science, Vol. 346, Issue 6207
https://doi.org/10.1126/science.1245993

An implantable microdevice to perform high-throughput in vivo drug sensitivity testing in tumors
journal, April 2015

Jonas, Oliver; Landry, Heather M.; Fuller, Jason E.
Science Translational Medicine, Vol. 7, Issue 284
https://doi.org/10.1126/scitranslmed.3010564

Modeling of Interactions between Cancer Stem Cells and their Microenvironment: Predicting Clinical Response
book, January 2018

Sehl, Mary E.; Wicha, Max S.
Methods in Molecular Biology
https://doi.org/10.1007/978-1-4939-7493-1_16

The evolution of tumour phylogenetics: principles and practice
journal, February 2017

Schwartz, Russell; Schäffer, Alejandro A.
Nature Reviews Genetics, Vol. 18, Issue 4
https://doi.org/10.1038/nrg.2016.170

Molecular characterization and targeted therapeutic approaches in breast cancer
journal, April 2015

Toss, Angela; Cristofanilli, Massimo
Breast Cancer Research, Vol. 17, Issue 1
https://doi.org/10.1186/s13058-015-0560-9

Translating neoadjuvant therapy into survival benefits: one size does not fit all
journal, March 2016

De Mattos-Arruda, Leticia; Shen, Ronglai; Reis-Filho, Jorge S.
Nature Reviews Clinical Oncology, Vol. 13, Issue 9
https://doi.org/10.1038/nrclinonc.2016.35

Biology of lung cancer: genetic mutation, epithelial-mesenchymal transition, and cancer stem cells
journal, July 2016

Aoi, Takashi
General Thoracic and Cardiovascular Surgery, Vol. 64, Issue 9
https://doi.org/10.1007/s11748-016-0682-8

Cancer systems biology: embracing complexity to develop better anticancer therapeutic strategies
journal, September 2014

Du, W.; Elemento, O.
Oncogene, Vol. 34, Issue 25
https://doi.org/10.1038/onc.2014.291

Genome evolution in ductal carcinoma in situ : invasion of the clones: DCIS genome evolution
journal, November 2016

Casasent, Anna K.; Edgerton, Mary; Navin, Nicholas E.
The Journal of Pathology, Vol. 241, Issue 2
https://doi.org/10.1002/path.4840

Heterogeneity in Malignant Pleural Mesothelioma
journal, May 2018

Oehl, Kathrin; Vrugt, Bart; Opitz, Isabelle
International Journal of Molecular Sciences, Vol. 19, Issue 6
https://doi.org/10.3390/ijms19061603

Minimal functional driver gene heterogeneity among untreated metastases
journal, September 2018

Reiter, Johannes G.; Makohon-Moore, Alvin P.; Gerold, Jeffrey M.
Science, Vol. 361, Issue 6406
https://doi.org/10.1126/science.aat7171

The dynamic control of signal transduction networks in cancer cells
journal, August 2015

Kolch, Walter; Halasz, Melinda; Granovskaya, Marina
Nature Reviews Cancer, Vol. 15, Issue 9
https://doi.org/10.1038/nrc3983

In situ single-cell analysis identifies heterogeneity for PIK3CA mutation and HER2 amplification in HER2-positive breast cancer
journal, August 2015

Janiszewska, Michalina; Liu, Lin; Almendro, Vanessa
Nature Genetics, Vol. 47, Issue 10
https://doi.org/10.1038/ng.3391

Spatially resolved transcriptomics and beyond
journal, December 2014

Crosetto, Nicola; Bienko, Magda; van Oudenaarden, Alexander
Nature Reviews Genetics, Vol. 16, Issue 1
https://doi.org/10.1038/nrg3832

Leveraging single cell RNA sequencing experiments to model intra-tumor heterogeneity
journal, September 2018

Ferrall-Fairbanks, Meghan C.; Ball, Markus; Padron, Eric
JCO Clinical Cancer Informatics
https://doi.org/10.1101/427047

Modeling differentiation-state transitions linked to therapeutic escape in triple-negative breast cancer
journal, March 2019

Chapman, Margaret P.; Risom, Tyler; Aswani, Anil J.
PLOS Computational Biology, Vol. 15, Issue 3
https://doi.org/10.1371/journal.pcbi.1006840

Computational Cancer Biology: An Evolutionary Perspective
text, January 2016

Beerenwinkel, Niko; Greenman, Chris D.; Lagergren, Jens
ETH Zurich
https://doi.org/10.3929/ethz-b-000114046

An emerging allee effect is critical for tumor initiation and persistence
text, January 2015

Böttger, Katrin; Hatzikirou, Haralambos; Voss-Böhme, Anja
Public Library of Science (PLoS)
https://doi.org/10.5167/uzh-189902

Initiation of aberrant DNA methylation patterns and heterogeneity in precancerous lesions of human hepatocellular cancer
audiovisual, January 2017

Hlady, Ryan A.; Zhou, Dan; Puszyk, William
Taylor & Francis
https://doi.org/10.6084/m9.figshare.4524875.v2

Cancer Evolution: Mathematical Models and Computational Inference
text, January 2015

Beerenwinkel, Niko; Schwarz, Roland F.; Gerstung, Moritz
ETH Zurich
https://doi.org/10.3929/ethz-b-000095953

Heterogeneity in Malignant Pleural Mesothelioma
text, January 2018

Oehl, Kathrin; Vrugt, Bart; Opitz, Isabelle
MDPI Publishing
https://doi.org/10.5167/uzh-153274

Initiation of aberrant DNA methylation patterns and heterogeneity in precancerous lesions of human hepatocellular cancer
audiovisual, January 2017

Hlady, Ryan A.; Zhou, Dan; Puszyk, William
Taylor & Francis
https://doi.org/10.6084/m9.figshare.4524875

Initiation of aberrant DNA methylation patterns and heterogeneity in precancerous lesions of human hepatocellular cancer
audiovisual, January 2017

Hlady, Ryan A.; Zhou, Dan; Puszyk, William
Taylor & Francis
https://doi.org/10.6084/m9.figshare.4524875.v1

JARID1B Is a Luminal Lineage-Driving Oncogene in Breast Cancer
journal, June 2014

Yamamoto, Shoji; Wu, Zhenhua; Russnes, Hege G.
Cancer Cell, Vol. 25, Issue 6
https://doi.org/10.1016/j.ccr.2014.04.024

Clinical significance of intratumor heterogeneity for gynecological carcinoma
journal, March 2015

Yang, Ying‐Chao; Li, Xiao‐Ping
Chronic Diseases and Translational Medicine, Vol. 1, Issue 1
https://doi.org/10.1016/j.cdtm.2015.02.005

Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression
journal, January 2018

Márquez-Jurado, Silvia; Díaz-Colunga, Juan; das Neves, Ricardo Pires
Nature Communications, Vol. 9, Issue 1
https://doi.org/10.1038/s41467-017-02787-4

Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer
journal, May 2018

Stover, Daniel G.; Gil Del Alcazar, Carlos R.; Brock, Jane
npj Breast Cancer, Vol. 4, Issue 1
https://doi.org/10.1038/s41523-018-0060-z

Clinical implications of changes in the diversity of c-MYC copy number variation after neoadjuvant chemotherapy in breast cancer
journal, November 2018

Chung, Yul Ri; Kim, Hyun Jeong; Kim, Milim
Scientific Reports, Vol. 8, Issue 1
https://doi.org/10.1038/s41598-018-35072-5

A pan-cancer signature of neutral tumor evolution
journal, February 2015

Sottoriva, Andrea; Graham, Trevor A.
Nature Genetics
https://doi.org/10.1101/014894

Reduction of LOXL2-mediated H3K4 oxidation increases chromatin accessibility and promotes chemosensitivity of triple-negative breast cancer cells
posted_content, September 2018

Cebria-Costa, J. P.; Pascual-Reguant, L.; Gonzalez-Perez, A.
BioRxiv
https://doi.org/10.1101/416495

Statistical measures of transcriptional diversity capture genomic heterogeneity of cancer
journal, October 2014

Jiang, Tingting; Shi, Weiwei; Natowicz, René
BMC Genomics, Vol. 15, Issue 1
https://doi.org/10.1186/1471-2164-15-876

Breast cancer intra-tumor heterogeneity
journal, May 2014

Martelotto, Luciano G.; Ng, Charlotte KY; Piscuoglio, Salvatore
Breast Cancer Research, Vol. 16, Issue 3
https://doi.org/10.1186/bcr3658

Cathepsin K induces platelet dysfunction and affects cell signaling in breast cancer - molecularly distinct behavior of cathepsin K in breast cancer
journal, March 2016

Andrade, Sheila Siqueira; Gouvea, Iuri Estrada; Silva, Mariana Cristina C.
BMC Cancer, Vol. 16, Issue 1
https://doi.org/10.1186/s12885-016-2203-7

The impact of pharmacokinetic gene profiles across human cancers
journal, May 2018

Zimmermann, Michael T.; Therneau, Terry M.; Kocher, Jean-Pierre A.
BMC Cancer, Vol. 18, Issue 1
https://doi.org/10.1186/s12885-018-4345-2

Intra-tumor heterogeneity from a cancer stem cell perspective
journal, February 2017

Prasetyanti, Pramudita R.; Medema, Jan Paul
Molecular Cancer, Vol. 16, Issue 1
https://doi.org/10.1186/s12943-017-0600-4

Molecular characterization and targeted therapeutic approaches in breast cancer
journal, April 2015

Toss, Angela; Cristofanilli, Massimo
Breast Cancer Research, Vol. 17, Issue 1
https://doi.org/10.1186/s13058-015-0560-9

GoIFISH: a system for the quantification of single cell heterogeneity from IFISH images
journal, August 2014

Trinh, Anne; Rye, Inga H.; Almendro, Vanessa
Genome Biology, Vol. 15, Issue 8
https://doi.org/10.1186/s13059-014-0442-y

Cancer genomics: one cell at a time
journal, August 2014

Navin, Nicholas E.
Genome Biology, Vol. 15, Issue 8
https://doi.org/10.1186/s13059-014-0452-9

Leveraging Single-Cell RNA Sequencing Experiments to Model Intratumor Heterogeneity
journal, December 2019

Ferrall-Fairbanks, Meghan C.; Ball, Markus; Padron, Eric
JCO Clinical Cancer Informatics, Issue 3
https://doi.org/10.1200/cci.18.00074

Modeling differentiation-state transitions linked to therapeutic escape in triple-negative breast cancer
journal, March 2019

Chapman, Margaret P.; Risom, Tyler; Aswani, Anil J.
PLOS Computational Biology, Vol. 15, Issue 3
https://doi.org/10.1371/journal.pcbi.1006840

Addressing intra-tumoral heterogeneity and therapy resistance
journal, September 2016

Rybinski, Brad; Yun, Kyuson
Oncotarget, Vol. 7, Issue 44
https://doi.org/10.18632/oncotarget.11875

Functional Optical Imaging of Primary Human Tumor Organoids: Development of a Personalized Drug Screen
journal, June 2017

Walsh, Alex J.; Cook, Rebecca S.; Skala, Melissa C.
Journal of Nuclear Medicine, Vol. 58, Issue 9
https://doi.org/10.2967/jnumed.117.192534

Quantitative Spatial Analysis of Metabolic Heterogeneity Across in vivo and in vitro Tumor Models
journal, November 2019

Heaster, Tiffany M.; Landman, Bennett A.; Skala, Melissa C.
Frontiers in Oncology, Vol. 9
https://doi.org/10.3389/fonc.2019.01144

Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy
journal, September 2016

Belizário, José E.; Sangiuliano, Beatriz A.; Perez-Sosa, Marcela
Frontiers in Pharmacology, Vol. 7
https://doi.org/10.3389/fphar.2016.00312

Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine
journal, December 2016

Contreras, Alejandra V.; Cocom-Chan, Benjamin; Hernandez-Montes, Georgina
Frontiers in Physiology, Vol. 7
https://doi.org/10.3389/fphys.2016.00606

Dynamic Targeting in Cancer Treatment
journal, February 2019

Wang, Zhihui; Deisboeck, Thomas S.
Frontiers in Physiology, Vol. 10
https://doi.org/10.3389/fphys.2019.00096

Heterogeneity in Malignant Pleural Mesothelioma
journal, May 2018

Oehl, Kathrin; Vrugt, Bart; Opitz, Isabelle
International Journal of Molecular Sciences, Vol. 19, Issue 6
https://doi.org/10.3390/ijms19061603

Contribution of Epithelial Plasticity to Therapy Resistance
journal, May 2019

Santamaría, Patricia G.; Moreno-Bueno, Gema; Cano, Amparo
Journal of Clinical Medicine, Vol. 8, Issue 5
https://doi.org/10.3390/jcm8050676

BitPhylogeny: a probabilistic framework for reconstructing intra-tumor phylogenies
text, January 2015

Ke, Yuan,; Thomas, Sakoparnig,; Florian, Markowetz,
ETH Zurich
https://doi.org/10.3929/ethz-b-000100138

Computational Cancer Biology: An Evolutionary Perspective
text, January 2016

Beerenwinkel, Niko; Greenman, Chris D.; Lagergren, Jens
ETH Zurich
https://doi.org/10.3929/ethz-b-000114046

In silico analysis of DNA re-replication across a complete genome reveals cell-to-cell heterogeneity and genome plasticity
text, January 2021

Anna, Rapsomaniki, Maria; Stella, Maxouri,; Patroula, Nathanailidou,
ETH Zurich
https://doi.org/10.3929/ethz-b-000467164

Why one-size-fits-all vaso-modulatory interventions fail to control glioma invasion: in silico insights
preprint, January 2016

Alfonso, J. C. L.; Kohn-Luque, A.; Stylianopoulos, T.
arXiv
https://doi.org/10.48550/arxiv.1604.05082

Simulated Ablation for Detection of Cells Impacting Paracrine Signalling in Histology Analysis
preprint, January 2017

Taylor-King, Jake P.; Baratchart, Etienne; Dhawan, Andrew
arXiv
https://doi.org/10.48550/arxiv.1704.04454

An emerging allee effect is critical for tumor initiation and persistence
text, January 2015

Böttger, Katrin; Hatzikirou, Haralambos; Voss-Böhme, Anja
Public Library of Science (PLoS)
https://doi.org/10.5167/uzh-189902

Similar records in OSTI.GOV collections:

Genetic and phenotypic heterogeneity of human malignancies: Finding order in chaos

Journal Article Shackney, S; Shankey, T - Cytometry

The presence of cellular heterogeneity within human tumors has been recognized for many years. Current concepts regarding the clonal origin of human neoplasms, and recent advances in the study of successive genetic changes that occur during tumor evolution may now make it possible to understand in greater depth the biological and clinical implications of intra-tumor heterogeneity at both the phenotypic and genotypic levels. In order to explore these concepts further, and to better identify the potential contributions that flow and image cytometry can make to our understanding of tumor heterogeneity, a session of the 1994 ISAC Congress was dedicated tomore »« less
https://doi.org/10.1002/cyto.990210103
The genomic and epigenomic evolutionary history of papillary renal cell carcinomas

Journal Article Zhu, Bin; Poeta, Maria; Costantini, Manuela; ... - Nature Communications

Intratumor heterogeneity (ITH) and tumor evolution have been well described for clear cell renal cell carcinomas (ccRCC), but they are less studied for other kidney cancer subtypes. Here we investigate ITH and clonal evolution of papillary renal cell carcinoma (pRCC) and rarer kidney cancer subtypes, integrating whole-genome sequencing and DNA methylation data. In 29 tumors, up to 10 samples from the center to the periphery of each tumor, and metastatic samples in 2 cases, enable phylogenetic analysis of spatial features of clonal expansion, which shows congruent patterns of genomic and epigenomic evolution. In contrast to previous studies of ccRCC, inmore »« less
https://doi.org/10.1038/s41467-020-16546-5

Full Text Available
TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

Journal Article Wu, J; Gong, G; Cui, Y; ... - Medical Physics

Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitativemore »« less
https://doi.org/10.1118/1.4957513
Biomass yield in a genetically diverse Miscanthus sacchariflorus germplasm panel phenotyped at five locations in Asia, North America, and Europe

Journal Article Njuguna, Joyce; Clark, Lindsay; Anzoua, Kossonou; ... - Global Change Biology. Bioenergy

Abstract Miscanthus is a high‐yielding bioenergy crop that is broadly adapted to temperate and tropical environments. Commercial cultivation of Miscanthus is predominantly limited to a single sterile triploid clone of Miscanthus × giganteus , a hybrid between Miscanthus sacchariflorus and M. sinensis. To expand the genetic base of M. × giganteus , the substantial diversity within its progenitor species should be used for cultivar improvement and diversification. Here, we phenotyped a diversity panel of 605 M. sacchariflorus from six previously described genetic groups and 27 M. × giganteus genotypes for dry biomass yield and 16 yield‐component traits, in field trialsmore »« less
https://doi.org/10.1111/gcbb.13043
Genetic variation and radiation quality impact cancer promoting cellular phenotypes in response to HZE exposure

Journal Article Sridharan, Deepa; Enerio, Shiena; Wang, Chris; ... - Life Sciences in Space Research

There exists a wide degree of genetic variation within the normal human population which includes disease free individuals with heterozygote defects in major DNA repair genes. A lack of understanding of how this genetic variation impacts cellular phenotypes that inform cancer risk post heavy ion exposure poses a major limitation in developing personalized cancer risk assessment astronauts. We initiated a pilot study with Human Mammary Epithelial Cell strains (HMEC) derived from wild type, a p16 silenced derivative of wild type, and various genetic variants that were heterozygote for DNA repair genes; BRCA1, BRCA2 and ATM. Cells strains were exposed tomore »« less
Cited by 3
https://doi.org/10.1016/j.lssr.2018.10.002

Full Text Available

Similar Records

Title: Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

Abstract

Citation Formats

Prospective identification of tumorigenic breast cancer cells journal, March 2003

Cellular Heterogeneity and Molecular Evolution in Cancer journal, January 2013

Cell type-specific DNA methylation patterns in the human breast journal, September 2008

Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer journal, June 2006

Epithelial-mesenchymal transition, cancer stem cells and treatment resistance journal, January 2012

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing journal, January 2012

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling journal, May 2007

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657 journal, September 2012

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing journal, March 2012

Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas journal, April 2010

Tumor heterogeneity: biological implications and therapeutic consequences journal, January 1983

Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection journal, March 2012

Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer journal, September 2006

The CD44+/CD24-phenotype is enriched in basal-like breast tumors journal, June 2008

Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy journal, December 2012

Intravital imaging of metastatic behavior through a mammary imaging window journal, November 2008

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer journal, May 2011

Intrinsic Resistance of Tumorigenic Breast Cancer Cells to Chemotherapy journal, April 2008

The Prognostic Role of a Gene Signature from Tumorigenic Breast-Cancer Cells journal, January 2007

Genetic clonal diversity predicts progression to esophageal adenocarcinoma journal, March 2006

Intra-tumour heterogeneity: a looking glass for cancer? journal, April 2012

Different prognostic significance of Ki-67 change between pre- and post-neoadjuvant chemotherapy in various subtypes of breast cancer journal, November 2012

Cancer as an evolutionary and ecological process journal, November 2006

A Comprehensive Survey of Clonal Diversity Measures in Barrett's Esophagus as Biomarkers of Progression to Esophageal Adenocarcinoma journal, October 2010

High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma: Genetic Heterogeneity and HNSCC Outcome journal, May 2013

Tumour evolution inferred by single-cell sequencing journal, March 2011

Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation journal, November 2010

Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype journal, February 2010

Heterogeneity for Stem Cell-Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer journal, January 2010

Molecular portraits of human breast tumours journal, August 2000

Heterogeneity in breast cancer journal, October 2011

Overcoming Intrinsic Multidrug Resistance in Melanoma by Blocking the Mitochondrial Respiratory Chain of Slow-Cycling JARID1Bhigh Cells journal, June 2013

Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers journal, February 2008

The cell kinetics of human mammary cancers journal, May 1979

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations journal, April 2010

Molecular Definition of Breast Tumor Heterogeneity journal, March 2007

Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer journal, March 2010

The landscape of cancer genes and mutational processes in breast cancer journal, May 2012

Genetic heterogeneity and cancer drug resistance journal, April 2012

Intratumor Heterogeneity: Seeing the Wood for the Trees journal, March 2012

Overcoming Intrinsic Multidrug Resistance in Melanoma by Blocking the Mitochondrial Respiratory Chain of Slow-Cycling JARID1Bhigh Cells journal, June 2013

Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy journal, December 2012

Primary chemotherapy in locally advanced breast cancer (LABC): effects on tumour proliferative activity, bcl-2 expression and the relationship between tumour regression and biological markers journal, October 1998

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer journal, May 2011

Intravital imaging of metastatic behavior through a mammary imaging window journal, November 2008

Intra-tumour heterogeneity: a looking glass for cancer? journal, April 2012

Cell type-specific DNA methylation patterns in the human breast journal, September 2008

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling journal, May 2007

Cellular Heterogeneity and Molecular Evolution in Cancer journal, January 2013

Genome-Wide Functional Synergy between Amplified and Mutated Genes in Human Breast Cancer journal, November 2008

Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer journal, June 2006

The CD44+/CD24-phenotype is enriched in basal-like breast tumors journal, June 2008

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. journal, August 1998

Recommendations From an International Expert Panel on the Use of Neoadjuvant (Primary) Systemic Treatment of Operable Breast Cancer: An Update journal, April 2006

Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity journal, February 2017

Subclonal diversification of primary breast cancer revealed by multiregion sequencing journal, June 2015

Computational Cancer Biology: An Evolutionary Perspective journal, February 2016

Punctuated copy number evolution and clonal stasis in triple-negative breast cancer journal, August 2016

Tumorigenesis: it takes a village journal, July 2015

The shock of being united and symphiliosis: Another lesson from plants? journal, July 2014

Tunneling nanotubes: A bridge for heterogeneity in glioblastoma and a new therapeutic target? journal, May 2019

Tumour heterogeneity and the evolution of polyclonal drug resistance journal, July 2014

Reconstructing cancer karyotypes from short read data: the half empty and half full glass journal, November 2017

The biology of circulating tumor cells journal, June 2015

Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer journal, September 2018

The impact of pharmacokinetic gene profiles across human cancers journal, May 2018

Quantitative Spatial Analysis of Metabolic Heterogeneity Across in vivo and in vitro Tumor Models journal, November 2019

Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression journal, January 2018

Cancer-associated fibroblast compositions change with breast-cancer progression linking S100A4 and PDPN ratios with clinical outcome posted_content, January 2020

An analysis of genetic heterogeneity in untreated cancers journal, August 2019

Intra-tumor heterogeneity from a cancer stem cell perspective journal, February 2017

Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine journal, December 2016

Initiation of aberrant DNA methylation patterns and heterogeneity in precancerous lesions of human hepatocellular cancer journal, January 2017

Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state journal, April 2019

Identification of neutral tumor evolution across cancer types journal, January 2016

Understanding tumor ecosystems by single-cell sequencing: promises and limitations journal, December 2018

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy journal, April 2016

Prospective identification of tumorigenic breast cancer cells
journal, March 2003

Cellular Heterogeneity and Molecular Evolution in Cancer
journal, January 2013

Cell type-specific DNA methylation patterns in the human breast
journal, September 2008

Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
journal, June 2006

Epithelial-mesenchymal transition, cancer stem cells and treatment resistance
journal, January 2012

Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
journal, January 2012

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
journal, May 2007

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657
journal, September 2012

Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
journal, March 2012

Molecular analysis reveals a genetic basis for the phenotypic diversity of metaplastic breast carcinomas
journal, April 2010

Tumor heterogeneity: biological implications and therapeutic consequences
journal, January 1983

Genomic and mutational profiling of ductal carcinomas in situ and matched adjacent invasive breast cancers reveals intra-tumour genetic heterogeneity and clonal selection
journal, March 2012

Pharmacogenomic Predictor of Sensitivity to Preoperative Chemotherapy With Paclitaxel and Fluorouracil, Doxorubicin, and Cyclophosphamide in Breast Cancer
journal, September 2006

The CD44+/CD24-phenotype is enriched in basal-like breast tumors
journal, June 2008

Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy
journal, December 2012

Intravital imaging of metastatic behavior through a mammary imaging window
journal, November 2008

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
journal, May 2011

Intrinsic Resistance of Tumorigenic Breast Cancer Cells to Chemotherapy
journal, April 2008

The Prognostic Role of a Gene Signature from Tumorigenic Breast-Cancer Cells
journal, January 2007

Genetic clonal diversity predicts progression to esophageal adenocarcinoma
journal, March 2006

Intra-tumour heterogeneity: a looking glass for cancer?
journal, April 2012

Different prognostic significance of Ki-67 change between pre- and post-neoadjuvant chemotherapy in various subtypes of breast cancer
journal, November 2012

Cancer as an evolutionary and ecological process
journal, November 2006

A Comprehensive Survey of Clonal Diversity Measures in Barrett's Esophagus as Biomarkers of Progression to Esophageal Adenocarcinoma
journal, October 2010

High intratumor genetic heterogeneity is related to worse outcome in patients with head and neck squamous cell carcinoma: Genetic Heterogeneity and HNSCC Outcome
journal, May 2013

Tumour evolution inferred by single-cell sequencing
journal, March 2011

Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
journal, November 2010

Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype
journal, February 2010

Heterogeneity for Stem Cell-Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer
journal, January 2010

Molecular portraits of human breast tumours
journal, August 2000

Heterogeneity in breast cancer
journal, October 2011

Overcoming Intrinsic Multidrug Resistance in Melanoma by Blocking the Mitochondrial Respiratory Chain of Slow-Cycling JARID1Bhigh Cells
journal, June 2013

Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers
journal, February 2008

The cell kinetics of human mammary cancers
journal, May 1979

A Chromatin-Mediated Reversible Drug-Tolerant State in Cancer Cell Subpopulations
journal, April 2010

Molecular Definition of Breast Tumor Heterogeneity
journal, March 2007

Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer
journal, March 2010

The landscape of cancer genes and mutational processes in breast cancer
journal, May 2012

Genetic heterogeneity and cancer drug resistance
journal, April 2012

Intratumor Heterogeneity: Seeing the Wood for the Trees
journal, March 2012

Overcoming Intrinsic Multidrug Resistance in Melanoma by Blocking the Mitochondrial Respiratory Chain of Slow-Cycling JARID1Bhigh Cells
journal, June 2013

Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy
journal, December 2012

Primary chemotherapy in locally advanced breast cancer (LABC): effects on tumour proliferative activity, bcl-2 expression and the relationship between tumour regression and biological markers
journal, October 1998

An increase in cancer stem cell population after primary systemic therapy is a poor prognostic factor in breast cancer
journal, May 2011

Intravital imaging of metastatic behavior through a mammary imaging window
journal, November 2008

Intra-tumour heterogeneity: a looking glass for cancer?
journal, April 2012

Cell type-specific DNA methylation patterns in the human breast
journal, September 2008

MET Amplification Leads to Gefitinib Resistance in Lung Cancer by Activating ERBB3 Signaling
journal, May 2007

Cellular Heterogeneity and Molecular Evolution in Cancer
journal, January 2013

Genome-Wide Functional Synergy between Amplified and Mutated Genes in Human Breast Cancer
journal, November 2008

Evaluation of Ki-67 proliferation and apoptotic index before, during and after neoadjuvant chemotherapy for primary breast cancer
journal, June 2006

The CD44+/CD24-phenotype is enriched in basal-like breast tumors
journal, June 2008

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.
journal, August 1998

Recommendations From an International Expert Panel on the Use of Neoadjuvant (Primary) Systemic Treatment of Operable Breast Cancer: An Update
journal, April 2006

Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity
journal, February 2017

Subclonal diversification of primary breast cancer revealed by multiregion sequencing
journal, June 2015

Computational Cancer Biology: An Evolutionary Perspective
journal, February 2016

Punctuated copy number evolution and clonal stasis in triple-negative breast cancer
journal, August 2016

Tumorigenesis: it takes a village
journal, July 2015

The shock of being united and symphiliosis: Another lesson from plants?
journal, July 2014

Tunneling nanotubes: A bridge for heterogeneity in glioblastoma and a new therapeutic target?
journal, May 2019

Tumour heterogeneity and the evolution of polyclonal drug resistance
journal, July 2014

Reconstructing cancer karyotypes from short read data: the half empty and half full glass
journal, November 2017

The biology of circulating tumor cells
journal, June 2015

Differentiation-state plasticity is a targetable resistance mechanism in basal-like breast cancer
journal, September 2018

The impact of pharmacokinetic gene profiles across human cancers
journal, May 2018

Quantitative Spatial Analysis of Metabolic Heterogeneity Across in vivo and in vitro Tumor Models
journal, November 2019

Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression
journal, January 2018

Cancer-associated fibroblast compositions change with breast-cancer progression linking S100A4 and PDPN ratios with clinical outcome
posted_content, January 2020

An analysis of genetic heterogeneity in untreated cancers
journal, August 2019

Intra-tumor heterogeneity from a cancer stem cell perspective
journal, February 2017

Host-Microbiome Interaction and Cancer: Potential Application in Precision Medicine
journal, December 2016

Initiation of aberrant DNA methylation patterns and heterogeneity in precancerous lesions of human hepatocellular cancer
journal, January 2017

Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state
journal, April 2019

Identification of neutral tumor evolution across cancer types
journal, January 2016

Understanding tumor ecosystems by single-cell sequencing: promises and limitations
journal, December 2018

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy
journal, April 2016

Clinical implications of changes in the diversity of c-MYC copy number variation after neoadjuvant chemotherapy in breast cancer
journal, November 2018

Interrogating open issues in cancer precision medicine with patient-derived xenografts
journal, January 2017

Breast Cancer Heterogeneity: Roles in Tumorigenesis and Therapeutic Implications
journal, February 2017