Mutational analysis of late-stage endometrioid endometrial carcinoma exomes

Endometrioid endometrial carcinomas (EECs) represent the majority of endometrial cancer (EC) diagnoses and have a 5-year overall survival rate of 83%. While most EEC patients are recognized early and have favorable outcomes, 14% are diagnosed late with stage III or stage IV disease; comparatively these patients have a poorer prognosis with 5-year overall survival rates of 68% and 26%, respectively. The genomic etiology of early-stage EEC has been well characterized. In this study we sought to identify mutated driver genes in late-stage EEC. We exome sequenced 19 late-stage EECs and identified 4492 somatic variants affecting 2919 protein-coding genes. The most frequently mutated genes were PTEN (84%), ARID1A (68%), PIK3CA (42%) and CTCF (37%), which have established roles in EEC. Using MutSigCV we identified 12 statistically significantly mutated genes (q-value