期刊
JOURNAL OF PATHOLOGY
卷 223, 期 5, 页码 567-573出版社
WILEY
DOI: 10.1002/path.2848
关键词
endometrial carcinoma; ovarian carcinoma; PPP2R1A; PP2A; high-grade serous; mutations; uterine carcinoma
资金
- British Columbia (BC) Cancer Foundation
- Vancouver General Hospital (VGH)-University of British Columbia Hospital Foundation
- Canadian Institutes of Health Research (CIHR)
- OvCaRe
- Ovarian Cancer Canada (VGH
- Banque de Tissus et de Donnees of the Reseau de Recherche sur le Cancer of the Fonds de la Recherche en Sante du Quebec)
- US Army Medical Research and Materiel Command [DAMD17-O1-1-0729]
- Cancer Council Tasmania
- Cancer Foundation of Western Australia
- National Health and Medical Research Council of Australia
PPP2R1A mutations have recently been described in 3/42 (7%) of clear cell carcinomas of the ovary. PPP2R1A encodes the alpha-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. (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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