Emphasizing the role of AKT pathway in endometrial cancer

AKT1 (E17K) mutation was originally found in breast (8%), colorectal (6%) and ovarian cancers (2%) and characterized for its clinical responsiveness to allosteric kinase inhibitor. Here, we sequenced 123 genes in 41 primary endometrial cancer and found 39% and 22% somatic mutations in PTEN and PIK3CA, respectively, along with two samples with mutations in the catalytic and regulatory domain of AKT2 (D399N) and AKT3 (E438D), respectively. Struck by Shoji et. al’s finding with AKT1 activating mutations in endometrial cancer, we reanalyzed our data with improved mutation detection algorithm. We find additional incidence of AKT1 (E17K) and AKT2 (R368C) mutation at residues conserved across species in the pleckstrin homology domain and catalytic domain, respectively. These mutations were validated to be somatic in nature by mass spectrometric genotyping of the tumor and matched normal DNA, following an independent PCR amplification. Taken together, we find 4 samples with AKT family mutations out of 41endometrial carcinoma DNAs tested (10%).