Germline mutations in the vhl gene in patients presenting with phaeochromocytomas

• Published in: International journal of cancer Vol. 77; no. 3; pp. 337 - 340
• Main Authors: van der Harst, E., de Krijger, R. R., Dinjens, W. N. M., Weeks, L. E., Bonjer, H. J., Bruining, H. A., Lamberts, S. W. J., Koper, J. W.
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 29.07.1998; Wiley-Liss
• Subjects: Adrenal Gland Neoplasms - genetics; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adult; Aged; Biological and medical sciences; DNA - blood; Endocrinopathies; Exons; Female; Genes, Tumor Suppressor; Genetic Variation; Humans; Introns; Leukocytes; Ligases; Male; Malignant tumors; Medical sciences; Middle Aged; Mutation; Pheochromocytoma - genetics; Polymorphism, Single-Stranded Conformational; Proteins - genetics; Retrospective Studies; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Von Hippel-Lindau Tumor Suppressor Protein; Endocrinopathy; Secretory tumor; Human; Pheochromocytoma; Germ line; Adrenal medulla; Genetics; Malignant tumor; Mutation; Tumor suppressor gene
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19980729)77:3<337::AID-IJC5>3.0.CO;2-P

It has been shown that an appreciable percentage of patients presenting with primary, apparently sporadic phaeochromocytomas may in fact have von‐Hippel‐Lindau (VHL) disease. In order to investigate this, we retrospectively screened 68 patients, who had been operated on for phaeochromocytomas, for the presence of germline mutations in the vhl gene. DNA was isolated from peripheral‐blood leukocytes and used to screen the entire coding sequence and the intron‐exon boundaries of the vhl gene for mutations, using a PCR‐based SSCP strategy. When an abnormal pattern was found in the SSCP analysis, sequence analysis was carried out. We found SSC variants in the vhl gene in 8 of the 68 patients. Of 6 patients, 2 turned out to be related (an uncle and his nephew), and they carried the same mis‐sense mutation: R64P. In 4 other patients, mis‐sense mutations, P25L, L63P, G144Q and I147T, were also identified. None of these mutations has been described, and 3 of them (P25L, L63P and R64P) are located closer to the N terminus of the vhl protein than any reported vhl mutation. In the remaining 2 cases, the mutations were localized not in the coding sequence but in the intronic sequence (but not within splice‐sites), adjacent to the exon, so they were probably not related to the disease. Our results show that a relatively high proportion (6/68, or 8.8%), though not as high as the 20% reported earlier, of patients with apparently sporadic phaeochromocytomas may carry germline mutations in the vhl gene. Int. J. Cancer 77:337–340, 1998. © 1998 Wiley‐Liss, Inc.