U.S. Department of EnergyOffice of Scientific and Technical Information
Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer
Abstract
Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure ormore »
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- Life Sciences Division
- OSTI Identifier:
- 1004691
- Report Number(s):
- LBNL-4233E
TRN: US201104%%1029
- DOE Contract Number:
- DE-AC02-05CH11231
- Resource Type:
- Book
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59; AMPLIFICATION; BIOLOGICAL MARKERS; CELL CYCLE; CHROMATIN; DEREGULATION; DETECTION; DISEASES; DNA; GROWTH FACTORS; INSTABILITY; MAMMARY GLANDS; MANAGEMENT; MUTATIONS; NEOPLASMS; PATHOLOGY; TARGETS
Citation Formats
Spellman, Paul T, Heiser, Laura, and Gray, Joe W. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer. United States: N. p., 2009.
Web.
Spellman, Paul T, Heiser, Laura, & Gray, Joe W. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer. United States.
Spellman, Paul T, Heiser, Laura, and Gray, Joe W. 2009.
"Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer". United States. https://www.osti.gov/servlets/purl/1004691.
@article{osti_1004691,
title = {Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer},
author = {Spellman, Paul T and Heiser, Laura and Gray, Joe W},
abstractNote = {Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also reveal the molecular differences between cancer and normal that may be exploited to therapeutic benefit or that provide targets for molecular assays that may enable early cancer detection, and predict individual disease progression or response to treatment. This chapter reviews current and future directions in genome analysis and summarizes studies that provide insights into breast cancer pathophysiology or that suggest strategies to improve breast cancer management.},
doi = {},
url = {https://www.osti.gov/biblio/1004691},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Thu Jun 18 00:00:00 EDT 2009},
month = {Thu Jun 18 00:00:00 EDT 2009}
}