Pathogenic Germline PALB2 and RAD50 Variants in Patients With Relapsed Ewing Sarcoma

Approximately 10% of patients with Ewing sarcoma (EwS) have pathogenic germline variants. Here, we report two cases: first, a novel germline pathogenic variant in partner and localizer of BRCA2 (PALB2) in a patient with a late EwS relapse. Its impact on homologous recombination is demonstrated, and breast cancer risk is discussed. Second, we report a pathogenic germline variant in RAD50 in a patient with a rare prostate primary EwS and later concurrent relapsed EwS and therapy-related acute myeloid leukemia (tAML) with two rare KMT2A translocations. Understanding rare pathogenic germline variants and the impact on cancer behavior, response to treatment and treatment-associated toxicities is important for patients.