These authors contributed equally to this study.
Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas†
Article first published online: 7 MAR 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 223, Issue 5, pages 567–573, April 2011
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
No conflicts of interest were declared.
- Issue published online: 10 MAR 2011
- Article first published online: 7 MAR 2011
- Accepted manuscript online: 5 JAN 2011 07:10AM EST
- Manuscript Accepted: 22 DEC 2010
- Manuscript Revised: 20 DEC 2010
- Manuscript Received: 25 NOV 2010
- US Army Medical Research and Materiel Command. Grant Number: DAMD17-O1-1-0729
- endometrial carcinoma;
- ovarian carcinoma;
- high-grade serous;
- uterine carcinoma
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.