Latif F, Tory K, Gnarra J, Yao M, Duh F M, Orcutt M L, Stackhouse T, Kuzmin I, Modi W, Geil L
Laboratory of Immunobiology, National Cancer Institute-Frederick Cancer Research and Development Center (NCI-FCRDC), Frederick, MD 21702-1201.
Science. 1993 May 28;260(5112):1317-20. doi: 10.1126/science.8493574.
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.
通过定位克隆发现的一个基因已被鉴定为冯·希佩尔-林道（VHL）病肿瘤抑制基因。包含该基因的一个限制性片段在221个VHL家族中的28个中显示出重排。这些重排中的18个是由于候选基因中的缺失，包括三个大的非重叠缺失。在源自VHL患者和散发性肾细胞癌的细胞系中检测到基因内突变。VHL基因在进化上是保守的，编码两个广泛表达的转录本，大小约为6和6.5千碱基。推断的基因产物的部分序列与其他蛋白质无同源性，除了在布氏锥虫前循环表面膜糖蛋白中发现的一个酸性重复结构域。
