High chromosome instability identified by low-pass whole-genome sequencing assay is associated with TP53 copy loss and worse prognosis in BRCA1 germline mutation breast cancer.
Breast Cancer
; 29(1): 103-113, 2022 Jan.
Article
em En
| MEDLINE
| ID: mdl-34403063
ABSTRACT
BACKGROUND:
Though BRCA1 mutation is the most susceptible factor of breast cancer, its prognostic value is disputable. Here in this study, we use a novel method which based on whole-genome analysis to evaluate the chromosome instability (CIN) value and identified the potential relationship between CIN and prognosis of breast cancer patients with germline-BRCA1 mutation. MATERIALS ANDMETHODS:
Sanger sequencing or a 98-gene panel sequencing assay was used to screen for BRCA1 germline small mutations in 1151 breast cancer patients with high-risk factors. MLPA assay was employed to screen BRCA1 large genomic rearrangements in familial breast cancer patients with BRCA1 negative for small mutations. Thirty-two samples with unique BRCA1 germline mutation patterns were further subjected to CIN evaluation by LPWGS (low-pass whole-genome sequencing) technology.RESULTS:
Firstly, 113 patients with germline BRCA1 mutations were screened from the cohort. Further CIN analysis by the LPWGS assay indicated that CIN was independent from the mutation location or type of BRCA1. Patients with high CIN status had shorter disease-free survival rates (DFS) (HR = 6.54, 95% CI 1.30-32.98, P = 0.034). The TP53 copy loss was also characterized by LPWGS assay. The rates of TP53 copy loss in CIN high and CIN low groups were 85.71% (12/14) and 16.67% (3/18), respectively.CONCLUSION:
CIN-high is a prognostic factor correlated with shorter DFS and was independent with the germline BRCA1 mutation pattern. Higher CIN values were significantly correlated with TP53 copy loss in breast cancer patients with germline BRCA1 mutation. Our results revealed a reliable molecular parameter for distinguishing patients with poor prognosis from the BRCA1-mutated breast cancer patients.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Proteína Supressora de Tumor p53
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Mutação em Linhagem Germinativa
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Dosagem de Genes
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Proteína BRCA1
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Instabilidade Cromossômica
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article