title: 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.
authors: INSERM Unit 602, Villejuif, France.
authors: Farhad Haghighi
authors: FH
authors: Rad
authors: Ayhan
authors: A
authors: Ulusakarya
authors: Sophie
authors: S
authors: Gad
authors: Mathilde
authors: M
authors: Sibony
authors: Fabrice
authors: F
authors: Juin
authors: Stéphane
authors: S
authors: Richard
authors: David
authors: D
authors: Machover
authors: Georges
authors: G
authors: Uzan
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D004730:Endothelium, Vascular / Q000473:pathology; D004921:Erythropoietin / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000150:complications / Q000235:genetics* / Q000601:surgery; D008297:Male; D009154:Mutation; D009392:Nephrectomy; D011086:Polycythemia / Q000097:blood / Q000150:complications / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000473:pathology; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D004921:Erythropoietin; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human