Journal
CELL
Volume 149, Issue 5, Pages 979-993Publisher
CELL PRESS
DOI: 10.1016/j.cell.2012.04.024
Keywords
-
Categories
Funding
- Wellcome Trust [098051]
- Breakthrough Breast Cancer Research [ICGC 08/09]
- Wellcome Trust Clinical Research
- Wellcome Trust Senior Clinical Research [WT088340MA]
- Research Foundation - Flanders [FWO]
- National Research Council Canada
- EMBO
- International Human Frontier Science Program Organization
- Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research
- Norwegian Research Council
- The Norwegian Cancer Society
- The Radium Hospital Foundation
- Health Region South-East
- European Community [242006]
- Breast Cancer Somatic Genetics Study [BASIS]
- Wellcome Trust Sanger Institute
- Breakthrough Breast Cancer Unit
- ICGC Breast Cancer Working Group
- Oslo University Hospital
- United States National Cancer Institute Specialized Program Of Research Excellence [CA089393]
- Centre for Translational Genomics (CTAG)
- Department of Health via NIHR comprehensive Biomedical Research Centre
- NHS Foundation Trust, King's College London
- King's College Hospital NHS Foundation Trust
- BBSRC [BBS/E/T/000PR6193] Funding Source: UKRI
- MRC [MC_U105178806] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BBS/E/T/000PR6193] Funding Source: researchfish
- Medical Research Council [MC_U105178806] Funding Source: researchfish
Ask authors/readers for more resources
All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed kataegis,'' was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available