Ashley CW, et al. - In this analysis, researchers defined the mutational signatures of endometrioid and serous endometrial carcinomas (ECs), stratified into the four molecular subtypes, uterine carcinosarcomas, and matched primary and metastatic ECs. Whole-exome sequencing MC3 data were reanalyzed from primary endometrioid and serous carcinomas (n = 232) and uterine carcinosarcomas (n = 57) from The Cancer Genome Atlas (TCGA), and matched primary and metastatic ECs (n = 61, 26 patients), subjected to mutational signature analysis using deconstructSigs and correlated with clinicopathologic and genomic data. Findings revealed that the mutational processes underlying ECs vary from primary to metastatic ECs to tumors of the same molecular subtype of TCGA. It was noted that 15% of serous-like ECs have the defective homologous recombination DNA repair signature 3 (homologous recombination DNA repair deficiency (HRD)-related). Data reported that only a minority of copy-number high (serous-like) ECs exhibit genomics features of HRD and would likely benefit from HRD-directed therapies.