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Novel somatic mutations of the VHL gene in an erythropoietin‐producing renal carcinoma associated with secondary polycythemia and elevated circulating endothelial progenitor cells
Author(s) -
Rad Farhad Haghighi,
Ulusakarya Ayhan,
Gad Sophie,
Sibony Mathilde,
Juin Fabrice,
Richard Stéphane,
Machover David,
Uzan Georges
Publication year - 2008
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.21019
Subject(s) - somatic cell , cancer research , erythropoietin , progenitor cell , biology , renal cell carcinoma , germline mutation , carcinogenesis , mutation , stem cell , medicine , cancer , pathology , gene , endocrinology , genetics
Mutation of the VHL tumor suppressor gene is a frequent genetic event in the carcinogenesis of renal‐cell carcinoma (RCC). Circulating endothelial progenitor cells (EPCs) have important role in neoangiogenesis, and mobilization of these cells is induced by various growth factors including erythropoietin (EPO). With this regard, we analyzed a patient with EPO‐producing clear‐cell RCC and polycythemia. DNA extraction and sequencing analysis of the VHL gene were performed from the tumor and the adjacent normal renal tissue. Isolated and cultured circulating EPCs from the blood taken with phlebotomy were characterized by flow cytometry and immunofluorescence analysis. This RCC had two novel somatic mutations of the VHL gene, p.Leu128Pro and p.Asn131Lys. Culture of blood mononuclear cells revealed a strikingly high number of endothelial cell colonies derived from EPCs (nearly 10‐fold more than in controls). Elevated number of circulating EPCs seems to be related to high EPO production from RCC with novel double somatic mutation of the VHL gene in this patient. Am. J. Hematol., 2008. © 2007 Wiley‐Liss, Inc.