Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic
Författare
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.
Avdelning/ar
- Bröstcancer-genetik
- Tumörmikromiljö
- Create Health
- Lunds Melanomstudiegrupp
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Kirurgi, Lund
- Kliniska Vetenskaper, Helsingborg
- Avdelningen för klinisk genetik
- Kirurgi
- Avdelningen för translationell cancerforskning
Publiceringsår
2016-08
Språk
Engelska
Sidor
8-1532
Publikation/Tidskrift/Serie
Annals of Oncology
Volym
27
Issue
8
Dokumenttyp
Artikel i tidskrift
Förlag
Oxford University Press
Ämne
- Cancer and Oncology
Status
Published
Projekt
- Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
Forskningsgrupp
- Lund Melanoma Study Group
- Surgery
ISBN/ISSN/Övrigt
- ISSN: 1569-8041