IDENTIFICATION OF THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE
IDENTIFICATION OF THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE
复制标题
DOI：
10.1126/science.8493574
复制
发表时间：
1993-05-28
期刊：
影响因子：
56.9
通讯作者：
LERMAN, MI
中科院分区：
文献类型：
--
作者：
LATIF, F;TORY, K;LERMAN, MI
通过定位克隆发现的一个基因被鉴定为von Hippel-Lindau(VHL)病肿瘤抑制基因。在221个VHL家系中，有28个家系中含有该基因的限制性内切酶片段重排。这些重排中有18个是由于候选基因的缺失，包括三个大的不重叠的缺失。在来自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，大约6kb和6.5kb。推测的基因产物的部分序列与其他蛋白质没有同源性，除了在布氏锥虫原环膜糖蛋白中发现的一个酸性重复结构域。
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.