Åke Borg
Principal investigator
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
Author
Summary, in English
We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
Department/s
- Breastcancer-genetics
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Familial Breast Cancer
Publishing year
2016-06-02
Language
English
Pages
47-54
Publication/Series
Nature
Volume
534
Issue
7605
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Cancer and Oncology
- Medical Genetics
- Cell and Molecular Biology
Keywords
- Breast Neoplasms
- Cohort Studies
- DNA Mutational Analysis
- DNA Replication
- DNA, Neoplasm
- Female
- Genes, BRCA1
- Genes, BRCA2
- Genome, Human
- Genomics
- Humans
- Male
- Mutagenesis
- Mutation
- Mutation Rate
- Oncogenes
- Recombinational DNA Repair
Status
Published
Project
- Genomisk karakterisering av trippelnegativ bröstcancer (TNBC)
Research group
- Familial Breast Cancer
ISBN/ISSN/Other
- ISSN: 0028-0836