Your browser doesn't support javascript.
loading
Application of next-generation sequencing in detection of BRCA1/2 and homologous recombination repair pathway multi-genes germline mutation and correlation analysis / 中华预防医学杂志
Chinese Journal of Preventive Medicine ; (12): 302-311, 2022.
Article in Chinese | WPRIM | ID: wpr-935285
ABSTRACT

Objective:

To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population.

Methods:

This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test.

Results:

Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC).

Conclusion:

The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Breast Neoplasms / Cross-Sectional Studies / Germ-Line Mutation / BRCA1 Protein / Genetic Predisposition to Disease / BRCA2 Protein / High-Throughput Nucleotide Sequencing / Recombinational DNA Repair / Triple Negative Breast Neoplasms / Mutation Type of study: Diagnostic study / Observational study / Prevalence study / Prognostic study / Risk factors Limits: Female / Humans Language: Chinese Journal: Chinese Journal of Preventive Medicine Year: 2022 Type: Article

Similar

MEDLINE

...
LILACS

LIS

Full text: Available Index: WPRIM (Western Pacific) Main subject: Breast Neoplasms / Cross-Sectional Studies / Germ-Line Mutation / BRCA1 Protein / Genetic Predisposition to Disease / BRCA2 Protein / High-Throughput Nucleotide Sequencing / Recombinational DNA Repair / Triple Negative Breast Neoplasms / Mutation Type of study: Diagnostic study / Observational study / Prevalence study / Prognostic study / Risk factors Limits: Female / Humans Language: Chinese Journal: Chinese Journal of Preventive Medicine Year: 2022 Type: Article