IDENTIFICATION OF THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE

A gene discovered by positional cloning has been identified as the von Hippel-Lindau (VHL) disease tumor suppressor gene. A restriction frag ment encompassing the gene showed rearrangements in 28 of 221 VHL kind reds. Eighteen of these rearrangements were due to deletions in the ca ndidate gene, including three large nonoverlapping deletions. Intragen ic mutations were detected in cell lines derived from VHL patients and from sporadic renal cell carcinomas. The VHL gene is evolutionarily c onserved and encodes two widely expressed transcripts of approximately 6 and 6.5 kilobases. The partial sequence of the inferred gene produc t shows no homology to other proteins, except for an acidic repeat dom ain found in the procyclic surface membrane glycoprotein of Trypanosom a brucei.