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

Winter, C LU ; Nilsson, M P LU ; Olsson, E LU ; George, A M LU ; Chen, Y LU ; Kvist, A LU ; Törngren, T LU ; Vallon-Christersson, J LU orcid ; Hegardt, C LU and Häkkinen, J LU orcid , et al. (2016) In Annals of Oncology 27(8). p.8-1532
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of Oncology
volume
27
issue
8
pages
7 pages
publisher
Oxford University Press
external identifiers
  • pmid:27194814
  • scopus:84984976224
  • wos:000383182800022
ISSN
1569-8041
DOI
10.1093/annonc/mdw209
project
Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
language
English
LU publication?
yes
id
907d8aed-50bf-4bfe-84a6-19abfe865d4a
date added to LUP
2016-08-29 09:38:02
date last changed
2024-06-14 12:52:51
@article{907d8aed-50bf-4bfe-84a6-19abfe865d4a,
  abstract     = {{<p>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.</p><p>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.</p><p>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).</p><p>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.</p>}},
  author       = {{Winter, C and Nilsson, M P and Olsson, E and George, A M and Chen, Y and Kvist, A and Törngren, T and Vallon-Christersson, J and Hegardt, C and Häkkinen, J and Jönsson, G and Grabau, D and Malmberg, M and Kristoffersson, U and Rehn, M and Gruvberger-Saal, S K and Larsson, C and Borg, Å and Loman, N and Saal, L H}},
  issn         = {{1569-8041}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{8--1532}},
  publisher    = {{Oxford University Press}},
  series       = {{Annals of Oncology}},
  title        = {{Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic}},
  url          = {{http://dx.doi.org/10.1093/annonc/mdw209}},
  doi          = {{10.1093/annonc/mdw209}},
  volume       = {{27}},
  year         = {{2016}},
}