Abstract:
Objective Homologous recombination repair (HRR) genes play an important role in the carcinogenesis of ovarian cancer (OC). At present, the mutations in breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes are well-characterized in OC. However, the characterization of DNA-damage repair (DDR) genes in Chinese patients with OC, as well as the relationship between HRR mutations and clinical features remain unclear.
Methods From June 2019 to June 2020, 122 peripheral blood samples and 67 tumor tissue samples of OC patients were collected from Tianjin Medical University Cancer Institute & Hospital, respectively. All methods were performed under the permission of the hospital’s ethics committee. Mutations in 19 DDR-related genes, including HRR and mismatch repair (MMR) genes, were detected via next-generation sequencing.
Results Next generation sequencing results revealed that germline mutations were mainly concentrated in HRR genes (80.37%). The number of patients with germline HRR (gHRR) mutations was more than the number of patients with BRCA mutations (31.15% vs. 23.77%). Patients with gHRR mutations showed familial aggregation, serous adenocarcinoma, and platinum sensitivity. In tumor tissue, the most common somatic mutation is in the tumor protein p53 (TP53) gene, followed by mutations in HRR genes (39.39%). The number of patients with tumor HRR (tHRR) mutations was 5.97% greater than the number of patients with gHRR mutations. Patients with tHRR mutations not only shared the same characteristics as patients with gHRR mutations but also had a lower risk of recurrence.
Conclusions This study revealed characteristics of DDR mutations in Chinese OC patients and these findings suggest that the detection of mutations in DDR genes can guide the diagnosis and treatment of OC.
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