Mutation of PPP2R1A: a new clue in unveiling the pathogenesis of uterine serous carcinoma

Uterine carcinoma is composed mainly of two distinct types: serous and endometrioid. Uterine serous carcinoma, while not as common as endometrioid carcinoma, is a highly aggressive disease and is associated with high mortality. Although the molecular genetic alterations of uterine endometrioid carcinoma have been well established, molecular genetic changes in uterine serous carcinoma are largely unclear. Two recent papers have analysed PPP2R1A mutations among different types of gynaecological neoplasia. Both studies report a surprisingly high frequency of somatic mutations of PPP2R1A in uterine serous carcinomas. PPP2R1A encodes a scaffolding subunit of a major serine/threonine phosphatase, protein phosphatase 2A (PP2A), which plays a critical role in diverse cellular functions, including negative regulation of cellular proliferation and potential tumour suppression. As PPP2R1A is essential for the phosphatase activity of PP2A, this observation should create a new research road map toward elucidating how PPP2R1A mutations and alterations of the PP2A pathway contribute to the pathogenesis of uterine serous carcinoma.