Identifying the germline variation spectrum and predisposition genes in Chinese ovarian cancer using whole exome sequencing.

BACKGROUND

Next-generation sequencing (NGS) allows for the simultaneous sequencing of multiple cancer predisposition genes. We assessed the frequency and spectrum of germline variations in individuals with ovarian cancer (OC), using whole exome sequencing (WES).

METHODS

A total of 92 patients with OC, with or without a family history of cancer, were consecutively recruited between May 2020 and September 2023. Germline DNA was sequenced using WES.

RESULTS

Among the 12 canonical OC predisposition genes recommended by the National Comprehensive Cancer Network (NCCN) guidelines, 26 patients (28.26%) were found to have 28 pathogenic or likely pathogenic variations in 5 genes, including BRCA1 (n = 13), BRCA2 (n = 8), RAD51D (n = 4), BRIP1 (n = 2), and MSH2 (n = 1). Additionally, 24 patients (26.08%) harbored variants of uncertain significance (VUS) in canonical OC predisposition genes or other putative OC predisposition genes, including 3 loss of function variation: NM_001142548.1(RAD54L): c.1825C > T (p.Arg609Ter), NM_002907.3(RECQL): c.796C > T (p.Gln266Ter), and NM_001114132.2 (NBEAL1): c.5837dup (p.Tyr1946Ter). Moreover, we found that the detection rate of predisposition genes was correlated with a family history of malignancies and a personal history of other malignancies.

CONCLUSIONS

Using WES, we found that 28.26% of patients with OC had germline cancer-predisposing variations. WES substantially improved the detection rates of a wide spectrum of variations in OC patients and uncovered putative predisposition genes.