Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas: Mutational signature associated with MUTYH deficiency in cancers
Abstract
Abstract Germline alterations in DNA repair genes are implicated in cancer predisposition and can result in characteristic mutational signatures. However, specific mutational signatures associated with base excision repair ( BER ) defects remain to be characterized. Here, by analysing a series of colorectal cancers ( CRCs ) using exome sequencing, we identified a particular spectrum of somatic mutations characterized by an enrichment of C > A transversions in NpCpA or NpCpT contexts in three tumours from a MUTYH ‐associated polyposis ( MAP ) patient and in two cases harbouring pathogenic germline MUTYH mutations. In two series of adrenocortical carcinomas ( ACCs ), we identified four tumours with a similar signature also presenting germline MUTYH mutations. Taken together, these findings demonstrate that MUTYH inactivation results in a particular mutational signature, which may serve as a useful marker of BER ‐related genomic instability in new cancer types. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Authors:
-
[1];
- INSERM UMR-S1147, Personalized Medicine, Pharmacogenomics, Therapeutic Optimization, Université Paris Descartes, Paris France
- INSERM, Unité Mixte de Recherche (UMR) 1162, Génomique Fonctionnelle des Tumeurs Solides, Equipe Labellisée Ligue contre le Cancer Paris France; Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité Paris France; Université Paris 13, Sorbonne Paris Cité, Unité de Formation et de Recherche (UFR) Santé, Médecine, Biologie Humaine (SMBH) Bobigny France; Université Paris Diderot, Institut Universitaire d'Hématologie, Paris France
- Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos NM USA; Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos NM USA
- INSERM U1016, CNRS UMR 8104, Paris Descartes University, Institut Cochin, Paris France; Center for Rare Adrenal Diseases, Department of Endocrinology, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris France
- Department of Medical Oncology AP-HP, Hospital Saint-Antoine, Paris France; Université Pierre et Marie Curie (UMPC) Paris VI, Paris France
- Department of Pathology AP-HP, Hôpital Ambroise Paré, Paris France; EA 4340, Université de Versailles, Versailles France
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Laboratory Directed Research and Development (LDRD) Program
- OSTI Identifier:
- 1351189
- Alternate Identifier(s):
- OSTI ID: 1401046
- Report Number(s):
- LA-UR-16-21448
Journal ID: ISSN 0022-3417
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Pathology
- Additional Journal Information:
- Journal Volume: 242; Journal Issue: 1; Journal ID: ISSN 0022-3417
- Publisher:
- Wiley
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Biological Science
Citation Formats
Pilati, Camilla, Shinde, Jayendra, Alexandrov, Ludmil B., Assié, Guillaume, André, Thierry, Hélias-Rodzewicz, Zofia, Ducoudray, Romain, Le Corre, Delphine, Zucman-Rossi, Jessica, Emile, Jean-François, Bertherat, Jérôme, Letouzé, Eric, and Laurent-Puig, Pierre. Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas: Mutational signature associated with MUTYH deficiency in cancers. United States: N. p., 2017.
Web. doi:10.1002/path.4880.
Pilati, Camilla, Shinde, Jayendra, Alexandrov, Ludmil B., Assié, Guillaume, André, Thierry, Hélias-Rodzewicz, Zofia, Ducoudray, Romain, Le Corre, Delphine, Zucman-Rossi, Jessica, Emile, Jean-François, Bertherat, Jérôme, Letouzé, Eric, & Laurent-Puig, Pierre. Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas: Mutational signature associated with MUTYH deficiency in cancers. United States. https://doi.org/10.1002/path.4880
Pilati, Camilla, Shinde, Jayendra, Alexandrov, Ludmil B., Assié, Guillaume, André, Thierry, Hélias-Rodzewicz, Zofia, Ducoudray, Romain, Le Corre, Delphine, Zucman-Rossi, Jessica, Emile, Jean-François, Bertherat, Jérôme, Letouzé, Eric, and Laurent-Puig, Pierre. Wed .
"Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas: Mutational signature associated with MUTYH deficiency in cancers". United States. https://doi.org/10.1002/path.4880. https://www.osti.gov/servlets/purl/1351189.
@article{osti_1351189,
title = {Mutational signature analysis identifies MUTYH deficiency in colorectal cancers and adrenocortical carcinomas: Mutational signature associated with MUTYH deficiency in cancers},
author = {Pilati, Camilla and Shinde, Jayendra and Alexandrov, Ludmil B. and Assié, Guillaume and André, Thierry and Hélias-Rodzewicz, Zofia and Ducoudray, Romain and Le Corre, Delphine and Zucman-Rossi, Jessica and Emile, Jean-François and Bertherat, Jérôme and Letouzé, Eric and Laurent-Puig, Pierre},
abstractNote = {Abstract Germline alterations in DNA repair genes are implicated in cancer predisposition and can result in characteristic mutational signatures. However, specific mutational signatures associated with base excision repair ( BER ) defects remain to be characterized. Here, by analysing a series of colorectal cancers ( CRCs ) using exome sequencing, we identified a particular spectrum of somatic mutations characterized by an enrichment of C > A transversions in NpCpA or NpCpT contexts in three tumours from a MUTYH ‐associated polyposis ( MAP ) patient and in two cases harbouring pathogenic germline MUTYH mutations. In two series of adrenocortical carcinomas ( ACCs ), we identified four tumours with a similar signature also presenting germline MUTYH mutations. Taken together, these findings demonstrate that MUTYH inactivation results in a particular mutational signature, which may serve as a useful marker of BER ‐related genomic instability in new cancer types. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.},
doi = {10.1002/path.4880},
journal = {Journal of Pathology},
number = 1,
volume = 242,
place = {United States},
year = {Wed Mar 29 00:00:00 EDT 2017},
month = {Wed Mar 29 00:00:00 EDT 2017}
}
Free Publicly Available Full Text
Publisher's Version of Record
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 89 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
A mutational signature in gastric cancer suggests therapeutic strategies
journal, October 2015
- Alexandrov, Ludmil B.; Nik-Zainal, Serena; Siu, Hoi Cheong
- Nature Communications, Vol. 6, Issue 1
DNA repair dysregulation from cancer driver to therapeutic target
journal, November 2012
- Curtin, Nicola J.
- Nature Reviews Cancer, Vol. 12, Issue 12
Deciphering Signatures of Mutational Processes Operative in Human Cancer
journal, January 2013
- Alexandrov, Ludmil B.; Nik-Zainal, Serena; Wedge, David C.
- Cell Reports, Vol. 3, Issue 1
Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas
journal, March 2004
- Jones, S.; Lambert, S.; Williams, G. T.
- British Journal of Cancer, Vol. 90, Issue 8
8-oxoguanine causes spontaneous de novo germline mutations in mice
journal, April 2014
- Ohno, Mizuki; Sakumi, Kunihiko; Fukumura, Ryutaro
- Scientific Reports, Vol. 4, Issue 1
Clock-like mutational processes in human somatic cells
journal, November 2015
- Alexandrov, Ludmil B.; Jones, Philip H.; Wedge, David C.
- Nature Genetics, Vol. 47, Issue 12
Analysis of protein-coding genetic variation in 60,706 humans
journal, August 2016
- Lek, Monkol; Karczewski, Konrad J.; Minikel, Eric V.
- Nature, Vol. 536, Issue 7616
Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma
journal, May 2012
- Guichard, Cécile; Amaddeo, Giuliana; Imbeaud, Sandrine
- Nature Genetics, Vol. 44, Issue 6
Signatures of mutational processes in human cancer
journal, August 2013
- Alexandrov, Ludmil B.; Nik-Zainal, Serena; Wedge, David C.
- Nature, Vol. 500, Issue 7463
Adenoma development in familial adenomatous polyposis and MUTYH -associated polyposis: somatic landscape and driver genes : Adenoma development in FAP and
journal, November 2015
- Rashid, Mamunur; Fischer, Andrej; Wilson, Cathy H.
- The Journal of Pathology, Vol. 238, Issue 1
Understanding the origins of human cancer
journal, December 2015
- Alexandrov, L. B.
- Science, Vol. 350, Issue 6265
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
journal, May 2016
- Nik-Zainal, Serena; Davies, Helen; Staaf, Johan
- Nature, Vol. 534, Issue 7605
Integrated genomic characterization of adrenocortical carcinoma
journal, April 2014
- Assié, Guillaume; Letouzé, Eric; Fassnacht, Martin
- Nature Genetics, Vol. 46, Issue 6
Telomerase activation by genomic rearrangements in high-risk neuroblastoma
journal, October 2015
- Peifer, Martin; Hertwig, Falk; Roels, Frederik
- Nature, Vol. 526, Issue 7575
Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors
journal, April 2016
- Kim, Jaegil; Mouw, Kent W.; Polak, Paz
- Nature Genetics, Vol. 48, Issue 6
Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
journal, May 2016
- Zheng, Siyuan; Cherniack, Andrew D.; Dewal, Ninad
- Cancer Cell, Vol. 29, Issue 5
Reactive oxygen species: Biological stimuli of neuroblastoma cell response
journal, October 2005
- Marengo, Barbara; Raffaghello, Lizzia; Pistoia, Vito
- Cancer Letters, Vol. 228, Issue 1-2
Inherited variants of MYH associated with somatic G:C→T:A mutations in colorectal tumors
journal, January 2002
- Al-Tassan, Nada; Chmiel, Nikolas H.; Maynard, Julie
- Nature Genetics, Vol. 30, Issue 2
Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis
journal, January 2005
- Bai, H.
- Nucleic Acids Research, Vol. 33, Issue 2
Clinical Implications of the Colorectal Cancer Risk Associated With MUTYH Mutation
journal, August 2009
- Lubbe, Steven J.; Di Bernardo, Maria Chiara; Chandler, Ian P.
- Journal of Clinical Oncology, Vol. 27, Issue 24
MutYH (MYH) and colorectal cancer
journal, August 2005
- Sampson, J. R.; Jones, S.; Dolwani, S.
- Biochemical Society Transactions, Vol. 33, Issue 4
Comprehensive molecular characterization of human colon and rectal cancer
text, January 2012
- Libraries, The University of North Carolina at Chapel Hill University
- The University of North Carolina at Chapel Hill University Libraries
A mutational signature in gastric cancer suggests therapeutic strategies.
text, January 2015
- Alexandrov, Ludmil B.; Nik-Zainal Abidin, Serena; Siu, Hoi Cheong
- Apollo - University of Cambridge Repository
Deciphering signatures of mutational processes operative in human cancer.
text, January 2013
- Alexandrov, Ludmil B.; Nik-Zainal Abidin, Serena; Wedge, David C.
- Apollo - University of Cambridge Repository
Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
journal, August 2016
- Zheng, Siyuan; Cherniack, Andrew D.; Dewal, Ninad
- Cancer Cell, Vol. 30, Issue 2
Comprehensive molecular characterization of human colon and rectal cancer
journal, January 2013
- McCullough, A.
- Yearbook of Pathology and Laboratory Medicine, Vol. 2013
Signatures of mutational processes in human cancer.
text, January 2013
- Alexandrov, Ludmil B.; Nik-Zainal Abidin, Serena; Wedge, David C.
- Apollo - University of Cambridge Repository
Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
journalarticle, January 2016
- Nik-Zainal, Serena; Davies, Helen; Staaf, Johan
- Springer Science and Business Media LLC
Comprehensive Pan-Genomic Characterization of Adrenocortical Carcinoma
text, January 2016
- Zheng, Siyuan; Cherniack, Andrew D.; Dewal, Ninad
- Cell Press (Elsevier)
Analysis of protein-coding genetic variation in 60,706 humans
text, January 2016
- Aarno, Palotie,; A., Rivas, Manuel; Hong-Hee, Won,
- The University of North Carolina at Chapel Hill University Libraries
Works referencing / citing this record:
Mutagenicity of Helicobacter hepaticus infection in the lower bowel mucosa of 129/SvEv Rag2 −/‐ Il10 −/− gpt delta mice is influenced by sex
journal, April 2019
- Ge, Zhongming; Feng, Yan; Sheh, Alexander
- International Journal of Cancer, Vol. 145, Issue 4
Integrative genomic analysis identifies associations of molecular alterations to APOBEC and BRCA1/2 mutational signatures in breast cancer
journal, June 2019
- Trevino, Victor
- Molecular Genetics & Genomic Medicine, Vol. 7, Issue 8
NTHL1 and MUTYH polyposis syndromes: two sides of the same coin?: Base excision repair polyposis syndromes
journal, December 2017
- Weren, Robbert DA; Ligtenberg, Marjolijn JL; Geurts van Kessel, Ad
- The Journal of Pathology, Vol. 244, Issue 2
Mutation analysis of POLE gene in patients with early-onset colorectal cancer revealed a rare silent variant within the endonuclease domain with potential effect on splicing
journal, May 2019
- Lasabová, Zora; Kalman, Michal; Holubeková, Veronika
- Clinical and Experimental Medicine, Vol. 19, Issue 3
The landscape of genomic alterations across childhood cancers
journal, February 2018
- Gröbner, Susanne N.; Worst, Barbara C.; Weischenfeldt, Joachim
- Nature, Vol. 555, Issue 7696
Validating the concept of mutational signatures with isogenic cell models
journal, May 2018
- Zou, Xueqing; Owusu, Michel; Harris, Rebecca
- Nature Communications, Vol. 9, Issue 1
5-Fluorouracil treatment induces characteristic T>G mutations in human cancer
journal, October 2019
- Christensen, Sharon; Van der Roest, Bastiaan; Besselink, Nicolle
- Nature Communications, Vol. 10, Issue 1
Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice
journal, January 2020
- Rose Li, Yun; Halliwill, Kyle D.; Adams, Cassandra J.
- Nature Communications, Vol. 11, Issue 1
Adrenocortical carcinoma — towards genomics guided clinical care
journal, May 2019
- Crona, Joakim; Beuschlein, Felix
- Nature Reviews Endocrinology, Vol. 15, Issue 9
The repertoire of mutational signatures in human cancer
journal, February 2020
- Alexandrov, Ludmil B.; Kim, Jaegil; Haradhvala, Nicholas J.
- Nature, Vol. 578, Issue 7793
Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets
journal, April 2018
- Wedge, David C.; Gundem, Gunes; Mitchell, Thomas
- Nature Genetics, Vol. 50, Issue 5
Genomic footprints of dryland stress adaptation in Egyptian fat-tail sheep and their divergence from East African and western Asia cohorts
journal, December 2017
- Mwacharo, Joram M.; Kim, Eui-Soo; Elbeltagy, Ahmed R.
- Scientific Reports, Vol. 7, Issue 1
Scarcity of Recurrent Regulatory Driver Mutations in Colorectal Cancer Revealed by Targeted Deep Sequencing
journal, April 2019
- Poulos, Rebecca C.; Perera, Dilmi; Packham, Deborah
- JNCI Cancer Spectrum, Vol. 3, Issue 2
Quantification of somatic mutation flow across individual cell division events by lineage sequencing
journal, November 2018
- Brody, Yehuda; Kimmerling, Robert J.; Maruvka, Yosef E.
- Genome Research, Vol. 28, Issue 12
Base excision repair deficiency signatures implicate germline and somatic MUTYH aberrations in pancreatic ductal adenocarcinoma and breast cancer oncogenesis
journal, March 2019
- Thibodeau, My Linh; Zhao, Eric Y.; Reisle, Caralyn
- Molecular Case Studies, Vol. 5, Issue 2
Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors
journal, August 2018
- Anderson, Nathaniel D.; de Borja, Richard; Young, Matthew D.
- Science, Vol. 361, Issue 6405
Molecular Drivers of Potential Immunotherapy Failure in Adrenocortical Carcinoma
journal, April 2019
- Fiorentini, Chiara; Grisanti, Salvatore; Cosentini, Deborah
- Journal of Oncology, Vol. 2019
Portrait of a cancer: mutational signature analyses for cancer diagnostics
journal, May 2019
- Van Hoeck, Arne; Tjoonk, Niels H.; van Boxtel, Ruben
- BMC Cancer, Vol. 19, Issue 1
Mutational signatures: experimental design and analytical framework
journal, February 2020
- Koh, Gene; Zou, Xueqing; Nik-Zainal, Serena
- Genome Biology, Vol. 21, Issue 1
Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment
journal, June 2018
- Burns, Michael B.; Montassier, Emmanuel; Abrahante, Juan
- PLOS Genetics, Vol. 14, Issue 6
Molecular features of premenopausal breast cancers in Latin American women: Pilot results from the PRECAMA study
journal, January 2019
- Olivier, Magali; Bouaoun, Liacine; Villar, Stephanie
- PLOS ONE, Vol. 14, Issue 1
Advances in adrenal tumors 2018
journal, July 2018
- Crona, J.; Beuschlein, F.; Pacak, K.
- Endocrine-Related Cancer, Vol. 25, Issue 7
Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
journal, March 2018
- Mafficini, Andrea; Scarpa, Aldo
- Journal of Endocrinology, Vol. 236, Issue 3
Molecular features of premenopausal breast cancers in Latin American women: pilot results from the PRECAMA study
posted_content, August 2018
- Olivier, Magali; Bouaoun, Liacine; Villar, Stephanie
- PLOS ONE
Mutational signatures: experimental design and analytical framework.
text, January 2020
- Koh, Gene; Zou, Xueqing; Nik-Zainal, Serena
- Apollo - University of Cambridge Repository
The repertoire of mutational signatures in human cancer
text, January 2020
- Alexandrov, Ludmil B.; Kim, Jaegil; Haradhvala, Nicholas J.
- Apollo - University of Cambridge Repository
Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets
text, January 2018
- Wedge, Dc; Gundem, Gunes; Mitchell, Thomas
- Apollo - University of Cambridge Repository
Validating the concept of mutational signatures with isogenic cell models.
text, January 2018
- Zou, Xueqing; Owusu, Michel; Harris, Rebecca
- Apollo - University of Cambridge Repository
Mutational signatures: experimental design and analytical framework
text, January 2020
- Koh, Gene; Zou, Xueqing; Nik-Zainal, Serena
- Apollo - University of Cambridge Repository
Mutational signatures: experimental design and analytical framework.
text, January 2020
- Koh, Gene; Zou, Xueqing; Nik-Zainal Abidin, Serena
- Apollo - University of Cambridge Repository
Integrative genomic analysis identifies associations of molecular alterations to APOBEC and BRCA1/2 mutational signatures in breast cancer
journal, June 2019
- Trevino, Victor
- Molecular Genetics & Genomic Medicine, Vol. 7, Issue 8
Mutational signatures in tumours induced by high and low energy radiation in Trp53 deficient mice
journal, January 2020
- Rose Li, Yun; Halliwill, Kyle D.; Adams, Cassandra J.
- Nature Communications, Vol. 11, Issue 1
The repertoire of mutational signatures in human cancer
journal, February 2020
- Alexandrov, Ludmil B.; Kim, Jaegil; Haradhvala, Nicholas J.
- Nature, Vol. 578, Issue 7793
Genomic footprints of dryland stress adaptation in Egyptian fat-tail sheep and their divergence from East African and western Asia cohorts
journal, December 2017
- Mwacharo, Joram M.; Kim, Eui-Soo; Elbeltagy, Ahmed R.
- Scientific Reports, Vol. 7, Issue 1
Scarcity of Recurrent Regulatory Driver Mutations in Colorectal Cancer Revealed by Targeted Deep Sequencing
journal, April 2019
- Poulos, Rebecca C.; Perera, Dilmi; Packham, Deborah
- JNCI Cancer Spectrum, Vol. 3, Issue 2
Portrait of a cancer: mutational signature analyses for cancer diagnostics
journal, May 2019
- Van Hoeck, Arne; Tjoonk, Niels H.; van Boxtel, Ruben
- BMC Cancer, Vol. 19, Issue 1
Molecular features of premenopausal breast cancers in Latin American women: Pilot results from the PRECAMA study
journal, January 2019
- Olivier, Magali; Bouaoun, Liacine; Villar, Stephanie
- PLOS ONE, Vol. 14, Issue 1
Advances in adrenal tumors 2018
journal, July 2018
- Crona, J.; Beuschlein, F.; Pacak, K.
- Endocrine-Related Cancer, Vol. 25, Issue 7
Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer Genome Consortium
journal, March 2018
- Mafficini, Andrea; Scarpa, Aldo
- Journal of Endocrinology, Vol. 236, Issue 3
Validating the concept of mutational signatures with isogenic cell models.
text, January 2018
- Zou, Xueqing; Owusu, Michel; Harris, Rebecca
- Apollo - University of Cambridge Repository
Detection of Low-Frequency Mutations and Identification of Heat-Induced Artifactual Mutations Using Duplex Sequencing
journal, January 2019
- Ahn, Eun Hyun; Lee, Seung Hyuk
- International Journal of Molecular Sciences, Vol. 20, Issue 1