Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic
Open Access
- 18 May 2016
- journal article
- research article
- Published by Elsevier in Annals of Oncology
- Vol. 27 (8) , 1532-1538
Abstract
A mutation found in the BRCA1 or BRCA2 gene of a breast tumor could be either germline or somatically acquired. The prevalence of somatic BRCA1/2 mutations and the ratio between somatic and germline BRCA1/2 mutations in unselected breast cancer patients are currently unclear. Paired normal and tumor DNA was analyzed for BRCA1/2 mutations by massively parallel sequencing in an unselected cohort of 273 breast cancer patients from south Sweden. Deleterious germline mutations in BRCA1 (n = 10) or BRCA2 (n = 10) were detected in 20 patients (7%). Deleterious somatic mutations in BRCA1 (n = 4) or BRCA2 (n = 5) were detected in 9 patients (3%). Accordingly, about 1 in 9 breast carcinomas (11%) in our cohort harbor a BRCA1/2 mutation. For each gene, the tumor phenotypes were very similar regardless of the mutation being germline or somatically acquired, whereas the tumor phenotypes differed significantly between wild-type and mutated cases. For age at diagnosis, the patients with somatic BRCA1/2 mutations resembled the wild-type patients (median age at diagnosis, germline BRCA1: 41.5 years; germline BRCA2: 49.5 years; somatic BRCA1/2: 65 years; wild-type BRCA1/2: 62.5 years). In a population without strong germline founder mutations, the likelihood of a BRCA1/2 mutation found in a breast carcinoma being somatic was ∼1/3 and germline 2/3. This may have implications for treatment and genetic counseling.Keywords
Funding Information
- Swedish Cancer Society (2009/1537, 2010/800, 2010/1254, 2013/730, 2013/637, 2013/750, 2014/562)
- Swedish Research Council (2009-2712, 2011-3021, 2012-1747, 2012-1986)
- Swedish Foundation for Strategic Research
- Knut and Alice Wallenberg Foundation
- VINNOVA
- Governmental Funding of Clinical Research within National Health Service
- Swedish Breast Cancer Group
- Crafoord Foundation
- Lund University Medical Faculty
- Gunnar Nilsson Cancer Foundation
- Skane University Hospital Foundation
- BioCARE Research Program
- King Gustav Vth Jubilee Foundation
- Krapperup Foundation
- Mrs. Berta Kamprad Foundation
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