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

• Published in: American journal of hematology Vol. 83; no. 2; pp. 155 - 158
• Main Authors: Rad, Farhad Haghighi, Ulusakarya, Ayhan, Gad, Sophie, Sibony, Mathilde, Juin, Fabrice, Richard, Stéphane, Machover, David, Uzan, Georges
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-02-2008; Wiley-Liss; Wiley
• Subjects: Aged; Biological and medical sciences; Biotechnology; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - complications; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - surgery; Computer Science; Diseases of red blood cells; DNA, Neoplasm - genetics; DNA, Neoplasm - isolation & purification; Endothelium, Vascular - pathology; Erythropoietin - genetics; Hematologic and hematopoietic diseases; Humans; Kidney Neoplasms - blood; Kidney Neoplasms - complications; Kidney Neoplasms - genetics; Kidney Neoplasms - surgery; Kidneys; Life Sciences; Male; Medical sciences; Mutation; Nephrectomy; Nephrology. Urinary tract diseases; Polycythemia - blood; Polycythemia - complications; Polycythemia - genetics; Polycythemias; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells - cytology; Stem Cells - pathology; Tumors of the urinary system; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Kidney disease; Endothelial cell; Secondary; Urinary system disease; Erythropoietin; Hematology; Stem cell; Hemopathy; Malignant tumor; Somatic mutation; Polypeptide; Polycythemia; Kidney cancer; Cancer; Tumor suppressor gene
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/ajh.21019

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.