KAT6Aamplifications are associated with shorter progression-free survival and overall survival in patients with endometrial serous carcinoma

Somatic copy number alterations (CNA) are common in endometrial serous carcinoma (ESC). We used the Tumor Cancer Genome Atlas Pan Cancer dataset (TCGA Pan Can) to explore the impact of somatic CNA and gene expression levels (mRNA) of cancer-related genes in ESC. Results were correlated with clinico-pathologic parameters such as age of onset, disease stage, progression-free survival (PFS) and overall survival (OS) (n = 108). 1,449 genes with recurrent somatic CNA were identified, observed in 10% or more tumor samples. Somatic CNA and mRNA expression levels were highly correlated (r> = 0.6) for 383 genes. Among these, 45 genes were classified in the Tier 1 category of Cancer Genome Census-Catalogue of Somatic Mutations in Cancer. Eighteen of 45 Tier 1 genes had highly correlated somatic CNA and mRNA expression levels includingARNT,PIK3CA,TBLXR1,ASXL1,EIF4A2,HOOK3,IKBKB,KAT6A,TCEA1,KAT6B,ERBB2,BRD4,KEAP1,PRKACA,DNM2,SMARCA4,AKT2,SS18L1. Our results are in agreement with previously reported somatic CNA forERBB2,BRD4andPIK3Cin ESC. In addition,AKT2(p = 0.002) andKAT6A (p = 0.015) amplifications were more frequent in tumor samples from younger patients (<60), andCEBPA(p = 0.028) andMYC(p = 0.023) amplifications were more common with advanced (stage III and IV) disease stage. Patients with tumors carryingKAT6AandMYCamplifications had shorter PFS and OS. The hazard ratio (HR) ofKAT6Awas 2.82 [95 CI 1.12-7.07] for PFS and 3.87 [95 CI 1.28-11.68] for OS. The HR ofMYCwas 2.25 [95 CI 1.05-4.81] and 2.62[95 CI 1.07-6.41] for PFS and OS, respectively.