Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants.
Adult
Aged
Alleles
BRCA1 Protein
/ genetics
BRCA2 Protein
/ genetics
Biomarkers, Tumor
Breast Neoplasms
/ diagnosis
Female
Gene Frequency
Gene Silencing
Genetic Association Studies
Genetic Predisposition to Disease
Germ-Line Mutation
Humans
Loss of Heterozygosity
Middle Aged
Neoplasm Grading
Neoplasm Staging
Prevalence
Young Adult
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
16 10 2020
16 10 2020
Historique:
received:
23
03
2020
accepted:
15
09
2020
entrez:
17
10
2020
pubmed:
18
10
2020
medline:
29
6
2021
Statut:
epublish
Résumé
The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1,995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants.
Identifiants
pubmed: 33067557
doi: 10.1038/s42003-020-01301-9
pii: 10.1038/s42003-020-01301-9
pmc: PMC7567851
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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