title: Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic.
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.
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: C
authors.initials: C
authors.lastname: Winter
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Department of Oncology, Skåne University Hospital, Lund.
authors.forename: M P
authors.initials: MP
authors.lastname: Nilsson
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: E
authors.initials: E
authors.lastname: Olsson
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: A M
authors.initials: AM
authors.lastname: George
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: A
authors.initials: A
authors.lastname: Kvist
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: T
authors.initials: T
authors.lastname: Törngren
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund.
authors.forename: J
authors.initials: J
authors.lastname: Vallon-Christersson
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund.
authors.forename: C
authors.initials: C
authors.lastname: Hegardt
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: J
authors.initials: J
authors.lastname: Häkkinen
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: G
authors.initials: G
authors.lastname: Jönsson
authors.affiliation: Department of Pathology, Skåne University Hospital, Lund.
authors.forename: D
authors.initials: D
authors.lastname: Grabau
authors.affiliation: Department of Oncology, Skåne University Hospital, Lund.
authors.forename: M
authors.initials: M
authors.lastname: Malmberg
authors.affiliation: Department of Clinical Genetics.
authors.forename: U
authors.initials: U
authors.lastname: Kristoffersson
authors.affiliation: Department of Surgery, Lund University and Skåne University Hospital, Lund.
authors.forename: M
authors.initials: M
authors.lastname: Rehn
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund.
authors.forename: S K
authors.initials: SK
authors.lastname: Gruvberger-Saal
authors.affiliation: Lund University Cancer Center, Lund Department of Translational Cancer Research, Lund University, Lund, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Larsson
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund.
authors.forename: Å
authors.initials: Å
authors.lastname: Borg
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund Department of Oncology, Skåne University Hospital, Lund.
authors.forename: N
authors.initials: N
authors.lastname: Loman
authors.affiliation: Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund Lund University Cancer Center, Lund CREATE Health Strategic Centre for Translational Cancer Research, Lund University, Lund lao.saal@med.lu.se.
authors.forename: L H
authors.initials: LH
authors.lastname: Saal
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D013548:Sweden / Q000453:epidemiology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: breast cancer; carrier; germline; mutation; prevalence; somatic