Targeted sequencing of BRCA1 and BRCA2 across a large unselected breast cancer cohort suggests that one-third of mutations are somatic
(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.
(Less)
- author
- organization
-
- Breastcancer-genetics
- Tumor microenvironment
- Create Health
- Lund Melanoma Study Group (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Surgery (Lund)
- Clinical Sciences, Helsingborg
- Division of Clinical Genetics
- Surgery (research group)
- Division of Translational Cancer Research
- publishing date
- 2016-08
- 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
-
- scopus:84984976224
- wos:000383182800022
- pmid:27194814
- 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
- 2024-09-07 20:06:04
@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}}, }