Identification of the von Hippel-Lindau Disease Tumor Suppressor Gene

TLDR

The VHL gene is evolutionarily conserved, encoding two ~6–6.5 kb transcripts, and its partial sequence lacks homology to other proteins except for an acidic repeat domain similar to a Trypanosoma brucei surface glycoprotein. Positional cloning identified the VHL tumor suppressor gene, with rearrangements in 28 of 221 kindreds, 18 due to deletions (including three large nonoverlapping ones), and intragenic mutations found in VHL patient and sporadic renal carcinoma cell lines.

Abstract

A gene discovered by positional cloning has been identified as the von Hippel-Lindau (VHL) disease tumor suppressor gene. A restriction fragment encompassing the gene showed rearrangements in 28 of 221 VHL kindreds. Eighteen of these rearrangements were due to deletions in the candidate gene, including three large nonoverlapping deletions. Intragenic mutations were detected in cell lines derived from VHL patients and from sporadic renal cell carcinomas. The VHL gene is evolutionarily conserved and encodes two widely expressed transcripts of approximately 6 and 6.5 kilobases. The partial sequence of the inferred gene product shows no homology to other proteins, except for an acidic repeat domain found in the procyclic surface membrane glycoprotein of Trypanosoma brucei .