Novel somatic mutations of the VHL gene in an erythropoietin-producing renal carcinoma associated with secondary polycythemia and elevated circulating endothelial progenitor cells.

Abstract:

: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.

journal_name

Am J Hematol

authors

Rad FH,Ulusakarya A,Gad S,Sibony M,Juin F,Richard S,Machover D,Uzan G

doi

10.1002/ajh.21019

subject

Has Abstract

pub_date

2008-02-01 00:00:00

pages

155-8

issue

2

eissn

0361-8609

issn

1096-8652

journal_volume

83

pub_type

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