Multigene panel testing for hereditary breast and ovarian cancers: An analysis of 1303 BRCA-negative Chinese patients.

Abstract

Background: Identification of other breast cancer susceptibility genes, other than BRCA1/2, in hereditary breast and ovarian cancers (HBOC) using multigene panels could help to assess cancer risk in patients. The spectrum and frequency of variants are different across ethnicity, it is therefore imperative to identify other HBOC genes in Chinese patients. Methods: 1,303 high-risk patients (negative for BRCA1, BRCA2, TP53 and PTEN) were selected from Hong Kong Hereditary Breast Cancer Family Registry and subjected to 30-gene panel by next-generation sequencing (Color Genomics). All detected pathogenic mutations were further validated by bi-directional DNA sequencing and co-analyzed by our in-house developed bioinformatics pipeline. Results: Sixty-one pathogenic or likely pathogenic variants were identified (4.68%), which correspond to 12 different cancer predisposition genes. Majority of the carriers (77.05%) had early-onset of breast cancer (age <45), 29.51% had family members with breast cancer and 13.11% were triple-negative. The most common mutated genes were PALB2 (1.38%), RAD51D (0.84%) and ATM (0.77%). Moreover, over 29% of patients had variant of unknown significance (VUS) in these genes, which account for 323 types. Conclusions: Additional preventive measures and clinical management are recommended in 90% of the mutation-positive cases. Multigene panel testing is an alternative strategy in the diagnosis of HBOC, this could help to estimate the cancer risk and aid the development of effective treatments.