Abstract
Consistent with their assumed mechanism of action, PARP inhibitors show significant therapeutic efficacy in breast, ovarian and prostate cancer, which are the solid tumor types most often associated with loss of function of key homologous recombination genes. It is not known, however, how often other solid tumor types may be homologous recombination deficient. Specific DNA aberration profiles, genomic scars are induced by homologous recombination deficiency (HRD) and those could be used to assess the presence or absence of this DNA repair pathway aberration in a given tumor biopsy. We analyzed whether the various HRD associated mutational signatures are present in the whole genome and whole exome sequencing data of lung cancer in the TCGA cohorts and found evidence that a subset of those cases shows robust signs of HR deficiency. These clinical cases could be candidates for PARP inhibitor treatment and their prioritization for clinical trials could be achieved using next generation sequencing based mutational signatures.