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Subtype‐specific mutation of PPP2R1A in endometrial and ovarian carcinomas
Author(s) -
McConechy Melissa K,
Anglesio Michael S,
Kalloger Steve E,
Yang Winnie,
Senz Janine,
Chow Christine,
HeraviMoussavi Alireza,
Morin Gregg B,
MesMasson AnneMarie,
Carey Mark S,
McAlpine Jessica N,
Kwon Janice S,
Prentice Leah M,
Boyd Niki,
Shah Sohrab P,
Gilks C. Blake,
Huntsman David G
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2848
Subject(s) - serous fluid , biology , serous carcinoma , clear cell carcinoma , endometrium , carcinoma , cancer research , ovary , somatic cell , clear cell , ovarian carcinoma , pathology , oncology , ovarian cancer , cancer , genetics , medicine , gene , endocrinology , biochemistry
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.