Abstract 119P
Background
Homologous recombination (HR) is a DNA repair pathway of clinical interest due to the treatment of PARP inhibitors (PARPi). Previous studies showed elevated gene mutations and tumor mutational burden (TMB) in HR deficiency (HRD) patients, suggesting potential combination treatment of PARPi plus immunotherapy. Here, we investigate the prevalence of HRD and TMB in Chinese and Western cancer patients.
Methods
Next-generation sequencing data and clinical data were collected from 15337 TCGA pan-cancer patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 3677 Chinese pan-cancer patients (Chinese cohort). Both HRD mutation ratio and TMB were calculated on the two cohorts following the same criteria.
Results
In total, 848 (23%) of the 3677 Chinese patients had at least one mutation of HR genes (HRD group). The top 5 mutant HR-associated cancer types were bladder cancer, cervical cancer, endometrial cancer, head and neck cancer, and neuroendocrine tumor. In both cohorts, the top three mutant HR genes were the same, ATM, BRCA2, and ATR, with slightly different mutant ratios (8%, 5.5%, 4.6% in Chinese cohort; 4.3%, 3.7%, 3.3% in Western cohort). The Chinese cohort had a higher mutation frequency of HR genes than the Western cohort. In both cohorts, TMB was higher in the HRD group compared to non-HRD group. The top 3 cancer types with significant differences of TMB between HRD group and non-HRD group were different between the two cohorts (head and neck cancer, colorectal cancer, gastric cancer in Chinese cohort; bladder cancer, gastric cancer, melanoma in Western cohort). Within all patients of the two cohorts, there were more high-level TMB (score > 10) patients in HRD group than in non-HRD group (44.7% vs. 9.4%, p < 0.01).
Conclusions
Our study provided a landscape of HRD mutations in Chinese pan-cancer patients, which could be a valuable complement to TCGA dataset. Both in Chinese and Western cohorts, the higher TMB in HRD patients suggested potential efficacy from combination treatment of PARPi and 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.