Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic

Summary, in English

BACKGROUND: 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.

PATIENTS AND METHODS: 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.

RESULTS: 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).

CONCLUSIONS: 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.

• Author: C Winter; M P Nilsson; E Olsson; A M George; Y Chen; A Kvist; T Törngren; J Vallon-Christersson; C Hegardt; J Häkkinen; G Jönsson; D Grabau; M Malmberg; U Kristoffersson; M Rehn; S K Gruvberger-Saal; C Larsson; Å Borg; N Loman; L H Saal
• Department/s: Breastcancer-genetics; Tumor microenvironment; Create Health; Lund Melanoma Study Group; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation; Surgery (Lund); Clinical Sciences, Helsingborg; Division of Clinical Genetics; Surgery; Division of Translational Cancer Research
• Publishing year: 2016-08
• Language: English
• Pages: 8-1532
• Publication/Series: Annals of Oncology
• Volume: 27
• Issue: 8
• Links: http://dx.doi.org/10.1093/annonc/mdw209
• Document type: Journal article
• Publisher: Oxford University Press
• Topic: Cancer and Oncology
• Status: Published
• Project: Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
• Research group: Lund Melanoma Study Group; Surgery
• ISBN/ISSN/Other: ISSN: 1569-8041