MSH6 and sarcoma: The presence of multiple predicted pathogenic DDR gene germline mutations (ERCC4, ATM, FANCI, MSH6) in an early-onset sarcoma in our study suggests that multiple pathogenic mutations may have an additive effect towards sarcoma predisposition, a hypothesis supported by the ISKS in which an earlier age-at-diagnosis was correlated with the cumulative burden of multiple pathogenic mutations7.