Parikh AR, et al. - Researchers attempted to characterize DNA damage response (DDR)-defective gastrointestinal (GI) malignancies and to gain insights into genomic context and tumor mutational burden (TMB). Using hybrid-capture-based comprehensive genomic profiling including sequencing of 10 predefined DDR genes: ARID1A, ATM, ATR, BRCA1, BRCA2, CDK12, CHEK1, CHEK2, PALB2, and RAD51, they assayed tumor samples from 17,486 unique patients with advanced colorectal, gastroesophageal, or small bowel carcinomas. Findings corroborated that DDR defects were relatively common. They also found a link between the selected DDR defects and a high TMB in more than 20% of cases. This investigation represents the largest to assess selected DDR defects in tubular GI cancers.