Abstract 657P
Background
The DNA-damage repair (DDR) system is essential for the preservation of genomic stability. Deleterious somatic and germline mutations involved in DDR pathway confer sensitivity to poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitions and implicate prognosis. However, few data explored the spectrum of DDR pathways in Chinese patients with prostate cancer.
Methods
A total of 982 patients conducted genetic testing by next-sequencing (NGS) technology were used for screening. A hundred and eighty-seven DDR genes were analyzed. Deleterious mutations were defined as pathogenic or likely pathogenic alterations. Only patients with qualified tissue NGS results performed by 381- and 733 gene panel were included in the following study. Matched blood sample were used for germline detection. Data analyses were conducted by R 3.6.2.
Results
Overall, 131 patients were eligible for analysis. There were 44 (33.6%) patients harboring pathogenic or likely pathogenic mutations in DDR genes, of which 15 patients (34.1%) had germline variations. Frameshift mutation was among the most common mutation type, which accounting for 44%, followed by copy number loss and nonsense aberration, the proportion was 34.4% and 8.20%, respectively. The most frequently mutated genes were BRCA2 (n=7; 5.34%), CDK12 (n=6; 4.58%), ATM (N=5, 3.82%). The genomic landscape among patients with DDR alterations was different from patients with no DDR alterations, for example, the mutation rates of TP53, PTEN and ERG were higher in no DDR mutation group, while FGFR3, FRS2 and MDM2 were identified only in DDR mutation group. Further analysis indicated that DDR mutations had no correlation with PD-L1 level (P = 0.3). The median TMB in DDR genes alteration group was higher than that in DDR wide type group (4.84 vs 4.03), but there was no significant difference (P=0.081).
Conclusions
This study explored the mutation landscape of DDR alterations in Chinese patients with prostate cancer. Further analysis could focus on the relationship between DDR mutation and TMB level, which might indicate the treatment of immunotherapy.
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.