Germline mutations in Chinese ovarian cancer with or without breast cancer

Abstract

Background Ovarian and breast cancers are known to have significant genetic components. Considering the differences in the mutation spectrum across ethnicity, it is important to identify hereditary breast and ovarian cancer (HBOC) genes mutation in Chinese for clinical management. Methods Two cohorts of 451 patients with ovarian cancer only (OV) and 93 patients with both breast and ovarian (BROV) cancers were initially screened for BRCA1, BRCA2, TP53, and PTEN. 109 OV and 43 BROV patients with extensive clinical risk and were being tested negative, were then further characterized by 30‐gene panel analysis. Results Pathogenic BRCA1/2 variants were identified in 45 OV patients and 33 BROV patients, giving a prevalence of 10% and 35.5%, respectively. After the extended screening, mutations in other HBOC genes were identified in an additional 12.8% (14/109) of the OV cohort and 14% (6/43) in the BROV cohort. The most commonly mutated genes in the OV cohort were MSH2 (4.6%) while in the BROV cohort were MSH2 (4.7%) and PALB2 (4.7%). With this extended multigene testing strategy, pathogenic mutations were detected in 12.8% of OV patients (BRCAs: 10%; additional genes: 12.8%) and 40.9% (BRCAs: 35.5%; additional genes: 14%) of BROV patients. Conclusion Extended characterization of the contributions of HBOC genes to OV and BROV patients has significant impacts on further management in patients and their families, expanding the screening net for more asymptomatic individuals.

Next-generation sequencing-based analysis of homologous recombination repair gene variant in ovarian cancer

“…Moreover, figuring out the alterations of BRCA1/2 , especially germline mutation, is an effective way to identify the inherited risk of cancer and take preventive measures. Previous studies showed that about 8.6–24.5 % patients harbored g BRCA1/2 mutations, while 3.7–7.1 % patients presented s BRCA1/2 mutations [ 10 , [31] , [32] , [33] , [34] , [35] ]. Our study excluded the benign mutations and found the frequencies of g/s BRCA1/2 mutation were 18.55 % and 9.68 %.…”

Prevalence of germline mutations in cancer susceptibility genes in Chinese patients with renal cell carcinoma

“…As highly conserved DNA remodeling enzymes (58)(59)(60), FANCI and FANCM can activate the FA DNA repair pathway to maintain genomic stability. Patients with FA, characterized by the clinically and genetically heterogeneous syndrome of bone marrow failure, are predisposed with a predisposition to cancers (61)(62)(63)(64). Studies have shown that the loss of function of some FA genes (such as BRCA1 and BRCA2) by germline inactivation can result in familial breast cancer predisposition syndromes (65)(66)(67)(68)(69)(70).…”

Prevalence and clinical implications of germline mutations among Jordanian patients with ovarian cancer. The Jordanian exploratory cancer genetics (Jo‐ECAG) ovarian study

“…Following extended screening, mutations in other HBOC genes were identified in an additional 12.8% of the OV cohort and 14% in the BROV cohort. The most commonly mutated genes were MSH2 and PALB2 (Kwong et al, 2022 ). However, PALB2 was rarely encountered (0.21%) among a group of 1421 patients with ovarian cancer (Kotsopoulos et al, 2017 ).…”