PPP2R1A mutations are common in the serous type of endometrial cancer

Authors

  • Deepak C. Nagendra,

    1. Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, Michigan
    Search for more papers by this author
  • James Burke III,

    1. Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center, Savannah, Georgia
    Search for more papers by this author
  • G. Larry Maxwell,

    1. Division of Gynecologic Oncology, Walter Reed Army Medical Center, Washington, District of Columbia
    Search for more papers by this author
  • John I. Risinger

    Corresponding author
    1. Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University College of Human Medicine, Grand Rapids, Michigan
    • Department of Obstetrics Gynecology & Reproductive Biology, Michigan State University College of Human Medicine, 333 Bostwick Ave, Room 4019, Van Andel Institute, Grand Rapids, MI 49503.
    Search for more papers by this author

  • The authors declare that there are no conflicts of interest.

Abstract

Recently unbiased sequencing efforts identified PPP2R1A mutations in clear cell ovarian cancers (OCC). Similar mutations were also noted with high frequency in uterine serous carcinoma. Because the endometrium develops from the same developmental precursors we further examined the hypothesis that PPP2R1A mutations might also occur in diverse histologic subtypes of uterine cancer. We sequenced the PPP2R1A in 22 cell line models of uterine cancer and 10 primary cancers. We found no mutations in the cell lines originally derived from endometrioid (n = 13), undifferentiated (n = 3), clear cell (n = 1), and carcinosarcoma (n = 3) cancers. However, we found a CCC (Pro) to CGC (Arg) codon 179 mutation in the ACI-158 serous carcinoma cell line, a CCC (Pro) to CTC (Leu) in a primary serous carcinoma as well as a CGC (Arg) to CAC (His) codon 258 mutation in a poorly differentiated endometrioid cancer. We sequenced a large panel of endometrial malignancies (n = 181) and found 12 mutants. Importantly, we confirmed a high frequency of mutation in 8 of 25 (32%) serous carcinomas a subtype with well-recognized poor prognosis. Mutations were infrequent in endometrioid cancer and absent in clear cell and carcinosarcoma subtypes. The PPP2R1A mutation regions are conserved among species and known to interact with the regulatory subunits of the PP2A enzyme. PPP2R1A mutant endometrial cancers may represent good candidates for personalized drug therapies particularly for women with the lethal serous histologic variant of uterine cancer. © 2011 Wiley Periodicals, Inc.

Ancillary