Abstract 1964P
Background
PARP inhibitors has been recommended as the second-line treatment of metastatic castration–resistant prostate cancer with homologous recombination repair mutations (HRRm). We aimed to investigate the genomic characteristics of HRRm in Chinese prostate cancer patients.
Methods
Hybrid capture-based next-generation sequencing were performed with matched tumor tissue and whole blood sample from prostate cancer patients between May 2019 and April 2020. Deleterious somatic and germline alterations in whole-exon region from 23 homologous recombination genes were analyzed. Whole-exome sequencing data from SU2C-PCF cohort including 444 prostate cancers were downloaded from cBioPortal.
Results
In total, 231 prostate cancer patients were included in our analysis, among whom 60 patients (25.97%) carried germline or somatic variants in homologous recombination genes. Sixteen (6.93%) patients had germline mutations including BRCA2 (10, 4.33%), ATM (2, 0.87%), CHEK2 (2, 0.87%), BRCA1 (1, 0.43%) and PALB2 (1, 0.43%). Forty-eight (20.78%) patients carried somatic variants, among whom 27 (11.69%) patients had germline and somatic variants simultaneously. Somatic mutation occurred in CDK12 (27, 11.69%), BRCA2 (10, 4.33%), FANCA (6, 2.6%), ATM (5, 2.16%), ATR (4, 1.73%), CHEK2 (2, 0.87%), ABRAXAS1 (1, 0.43%) and RAD 51 (1, 0.43%). Comparing with SU2C-PCF cohort, germline mutation frequency was comparable between two cohorts, while somatic mutation frequency of CDK12 (5.8%), BRCA2 (2.46%) and FANCA (0.47%) detected in SU2C-PCF cohort was slightly lower. Furthermore, tumor mutation burden was significantly higher in tumors with HRRm comparing with HRR wildtype (median TMB, 4.47 vs 3.35 muts/Mb, P = 0.003). Median counts of small insertions or deletions was also higher in tumors with HRRm (median counts, 2 vs 1, P < 0.001).
Conclusions
About 25.97% of prostate cancers carried deleterious germline or somatic variants in genes involved in homologous recombination repair. Tumors with HRRm present nature of genomic instability. These findings might expand the number of patients benefiting from PARP inhibitors or platinum-based chemotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.