DNA damage repair (DDR) pathway defects in gastrointestinal (GI) malignancies.

647Background: The clinical significance of the genomic alterations associated with DDR pathway in GI tumors (besides MMR defects) is largely unknown. These patients can potentially derive benefit from targeted therapy with poly ADP ribose polymerase (PARP) inhibitors, which have already shown promising activity in ovarian, breast and prostate cancers. In this study, we investigated the frequency and clinical significance of DDR repair defects (other than MMR defects) in GI tumors. Methods: We performed a retrospective analysis of all patients who had tumor next generation sequencing performed between January 2013 and August 2017 on GI cancers harboring DDR pathway defects. Data including demographics, clinical history, and treatment were extracted from patients' records. Results: Of 299 patients with GI tumors sequenced, 35 cases (12%) were noted to have DDR defects. The most commonly mutated genes – 6 (17%) BRCA2, 5 (14%) PALB2, 4 (11%) ATM, 3 (8.6%) BRCA1, 2 (5.7%) each of NBN, MUTYH, ERCC3, PARP1 ampl...