Mutation patterns and prognostic potentiality of homologous recombination repair genes in gliomas

Gliomas are primary malignant brain tumors with poor prognosis. Conventional therapies have achieved limited improvements, and there is an urgent need for new treatments. Homologous recombination repair (HRR) defects are observed in many types of cancer and confer increased sensitivity to platinum-based chemotherapies and poly-ADP ribose polymerase (PARP) inhibitors. To our knowledge, HRR mutations in gliomas have not been extensively reported. To this end, we analyzed alterations in 39 HRR related genes and divided patients with glioma into different groups according to HRR LOF mutation status. We then analyzed the differences in genetic mutation landscape, TMB, CNV burden, prognosis, and immune-related features between the HRR-LOF group and the NonHRR-LOF group. The results demonstrated that compared to the non-HRR-LOF group, the HRR-LOF group exhibited a higher mutation frequency of IDH1, increased TMB, and poor prognosis in IDH-mutant patients. In summary, gliomas patients with HRR LOF have relatively more unstable genomes and might benefit from the combination and sequential use of PARP inhibitors, radiotherapy, and immunotherapy.