Abstract 103P
Background
PARP inhibitors' treatment has been shown to be beneficial in tumors with BRCA1/2 mutations and has already been approved for patients with ovarian, breast, pancreatic, and prostate cancer. The aim of the study was to access the utility of a multigene panel for the analysis of mutations in genes of the homologous recombination (HR) pathway as well as loss of heterozygosity (LOH), as predictors of treatment response.
Methods
Tumor molecular profile analysis was performed in 939 patients with various types of solid tumors. An NGS methodology was used, for the analysis of more than 500 cancer-related genes. The evaluation of genomic instability was performed through the analysis of HR gene mutations and the measurement of %LOH at the sample level.
Results
Mutations in the BRCA1/2 genes were detected in 3.09% of patients, while mutations in other HR genes were found in 10.65% of the cases. In prostate, ovarian, breast, and pancreatic cancers with approved PARP inhibitors available, the rates of HR mutation detection were significantly increased: 40%, 27%, 16%, and 10% respectively. Furthermore, in 201 patients the %LOH value was also calculated. The median LOH value obtained was 19.22%, with 44% of the samples showing high LOH values. Increased LOH rates were observed for breast and ovarian cancer (70% and 53% respectively), while in prostate and pancreatic cancer the LOH rates were lower (0% and 36% respectively). HR mutations were highly correlated with high %LOH in ovarian cancer since 50% of the cases with increased %LOH harbored a high-risk HR gene mutation. Except for ovarian cancer, the detection of HR mutations was not always accompanied by high LOH in the rest of the tumor types analyzed, since 53% of BRCA1/2-positive tumors and 60% of HR-positive tumors exhibited low LOH (Table). Table: 103P
HR gene mutation rate and LOH
| Tumor type histology | HR mutation + | LOH+ patients | BRCA+/LOH- patients | HR+/LOH- patients |
| Ovarian | 27% | 53% | 0% | 22% |
| Others | 12% | 44% | 53% | 60% |
Conclusions
The use of large gene panels allows the identification of mutations in the HR genes while giving an insight into the genomic instability of the tumor by measuring LOH.
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.