Germ-line mutations in the von Hippel-Lindau tumor-suppressor gene are similar to somatic von Hippel-Lindau aberrations in sporadic renal cell carcinoma

摘要: von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome predisposing to multifocal bilateral renal cell carcinomas (RCCs), pheochromocytomas, and pancreatic tumors, as well angiomas hemangioblastomas of the CNS. A candidate gene for VHL was recently identified, which led isolation partial cDNA clone with extended open reading frame, without significant homology known genes or obvious functional motifs, except an acidic pentamer repeat domain. To further characterize domains assess its involvement in nonhereditary we performed mutation analyses studied expression normal tissue. We identified germline mutations 39% families. Moreover, 33% sporadic RCCs all (6/6) RCC lines analyzed showed within gene. Both germ-line somatic included deletions, insertions, splice-site mutations, missense nonsense clustered at 3' end corresponding including alternatively spliced exon 123 nt length, suggesting functionally important encoded by this region. Over 180 tumors other types have shown no detectable base changes presumed coding sequence date. conclude that causing has specific role etiology RCCs, acts recessive tumor-suppressor gene, appears encode frame.