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

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Bibtex

@article{907d8aed50bf4bfe84a619abfe865d4a,
title = "Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic",
abstract = "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 and Nilsson, {M P} and E Olsson and George, {A M} and Y Chen and A Kvist and T T{\"o}rngren and J Vallon-Christersson and C Hegardt and J H{\"a}kkinen and G J{\"o}nsson and D Grabau and M Malmberg and U Kristoffersson and M Rehn and Gruvberger-Saal, {S K} and C Larsson and {\AA} Borg and N Loman and Saal, {L H}",
note = "{\circledC} The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.",
year = "2016",
month = "8",
doi = "10.1093/annonc/mdw209",
language = "English",
volume = "27",
pages = "1532--8",
journal = "Annals of Oncology",
issn = "1569-8041",
publisher = "Oxford University Press",
number = "8",

}