Original Paper

Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas†

  1. Melissa K McConechy1,‡,
  2. Michael S Anglesio1,‡,
  3. Steve E Kalloger2,
  4. Winnie Yang2,
  5. Janine Senz1,
  6. Christine Chow7,
  7. Alireza Heravi-Moussavi1,
  8. Gregg B Morin3,
  9. Anne-Marie Mes-Masson4,
  10. Australian Ovarian Cancer Study Group5,
  11. Mark S Carey6,
  12. Jessica N McAlpine6,
  13. Janice S Kwon6,
  14. Leah M Prentice2,
  15. Niki Boyd2,
  16. Sohrab P Shah1,
  17. C. Blake Gilks7,
  18. David G Huntsman1,7,*

Article first published online: 7 MAR 2011

DOI: 10.1002/path.2848

Issue

The Journal of Pathology

The Journal of Pathology

Volume 223, Issue 5, pages 567–573, April 2011

Additional Information

How to Cite

McConechy, M. K., Anglesio, M. S., Kalloger, S. E., Yang, W., Senz, J., Chow, C., Heravi-Moussavi, A., Morin, G. B., Mes-Masson, A.-M., Australian Ovarian Cancer Study Group, Carey, M. S., McAlpine, J. N., Kwon, J. S., Prentice, L. M., Boyd, N., Shah, S. P., Gilks, C. B. and Huntsman, D. G. (2011), Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas. J. Pathol., 223: 567–573. doi: 10.1002/path.2848

Author Information

  1. 1

    Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, BC, Canada

  2. 2

    Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, BC, Canada

  3. 3

    Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Department of Medical Genetics, University of BC, Vancouver, Canada

  4. 4

    Centre de Recherche CHUM et Institut du Cancer de Montréal Hôpital Notre-Dame, Université de Montréal, Montreal, Quebec, Canada

  5. 5

    Peter MacCallum Cancer Centre and the University of Melbourne, Victoria, Australia; Queensland Institute of Medical Research, Brisbane, Queensland, Australia; and Westmead Institute for Cancer Research, University of Sydney at the Westmead Millennium Institute, Sydney, Australia; Management Group, D. Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green and P. Webb

  6. 6

    Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada

  7. 7

    Genetic Pathology Evaluation Centre of the Prostate Research Centre and Department of Pathology, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada

  1. ‡

    These authors contributed equally to this study.

*Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Genetic Pathology Evaluation Centre of the Prostate Rearch Centre, 3427-600 West 10th Avenue, Vancouver BC V5E 4E6, Canada.

  1. †

    No conflicts of interest were declared.

  2. ‡

    These authors contributed equally to this study.

Publication History

  1. Issue published online: 10 MAR 2011
  2. Article first published online: 7 MAR 2011
  3. Accepted manuscript online: 5 JAN 2011 07:10AM EST
  4. Manuscript Accepted: 22 DEC 2010
  5. Manuscript Revised: 20 DEC 2010
  6. Manuscript Received: 25 NOV 2010

Funded by

  • US Army Medical Research and Materiel Command. Grant Number: DAMD17-O1-1-0729

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (194K)

Keywords:

  • endometrial carcinoma;
  • ovarian carcinoma;
  • PPP2R1A;
  • PP2A;
  • high-grade serous;
  • mutations;
  • uterine carcinoma

Abstract

PPP2R1A mutations have recently been described in 3/42 (7%) of clear cell carcinomas of the ovary. PPP2R1A encodes the α-isoform of the scaffolding subunit of the serine/threonine protein phosphatase 2A (PP2A) holoenzyme. This putative tumour suppressor complex is involved in growth and survival pathways. Through targeted sequencing of PPP2R1A, we identified somatic missense mutations in 40.8% (20/49) of high-grade serous endometrial tumours, and 5.0% (3/60) of endometrial endometrioid carcinomas. Mutations were also identified in ovarian tumours at lower frequencies: 12.2% (5/41) of endometrioid and 4.1% (2/49) of clear cell carcinomas. No mutations were found in 50 high-grade and 12 low-grade serous carcinomas. Amino acid residues affected by these mutations are highly conserved across species and are involved in direct interactions with regulatory B-subunits of the PP2A holoenzyme. PPP2R1A mutations in endometrial high-grade serous carcinomas are a frequent and potentially targetable feature of this disease. The finding of frequent PPP2R1A mutations in high-grade serous carcinoma of the endometrium but not in high-grade serous carcinoma of the ovary provides clear genetic evidence that these are distinct diseases. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

View Full Article with Supporting Information (HTML) Get PDF (194K)