Further to mutations in cancer genes already observed in uterine and ovarian CS such as TP53, PIK3CA, PPP2R1A, KRAS, PTEN, CHD4, and BCOR, this study identified an excess of mutations in genes encoding histone H2A and H2B, demonstrating a stable transgenic expression of H2A and H2B in a uterine serous carcinoma cell line. Here, PIK3CA is linked to endometrial serous adenocarcinoma.