VONHIPPEL-LINDAU DISEASE MAPS TO THE REGION OF CHROMOSOME-3 ASSOCIATED WITH RENAL-CELL CARCINOMA
VONHIPPEL-LINDAU DISEASE MAPS TO THE REGION OF CHROMOSOME-3 ASSOCIATED WITH RENAL-CELL CARCINOMA
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DOI：
10.1038/332268a0
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发表时间：
1988-03-17
期刊：
影响因子：
64.8
通讯作者：
GUSELLA, JF
中科院分区：
文献类型：
--
作者：
SEIZINGER, BR;ROULEAU, GA;GUSELLA, JF
Von Hippel-Lindau病（VHL）是一种常染色体显性遗传疾病，对各种形式的癌症具有遗传易感性，包括中枢神经系统血管母细胞瘤、嗜铬细胞瘤、胰腺恶性肿瘤和肾细胞癌1 -3。肾细胞癌构成了这种疾病中特别常见的死亡原因，作为双侧和多灶性肿瘤发生，并且比这种肿瘤类型的散发性、非家族性病例在更早的年龄出现。我们在此报告VHL基因与RAF 1癌基因的人类同源基因编码位点相连，该基因定位于染色体3 p25（参考文献4）。与VHL位点的交叉表明，VHL表型的缺陷不是RAF 1基因本身的突变。肿瘤形成中癌基因激活的替代或先前事件可能是推定的“肿瘤抑制因子”的失活，其可能与遗传性和散发性癌症形式相关。散发性肾细胞癌以前与染色体3 p区域的丢失有关（参考文献5，6）。因此，散发性和VHL相关形式的肾细胞癌可能都是由于该染色体上相同的“肿瘤抑制”基因功能丧失的改变引起的。
Von Hippel–Lindau disease (VHL) is an autosomal dominant disorder with inherited susceptibility to various forms of cancer, including hemangioblastomas of the central nervous system, phaeochromocytomas, pancreatic malignancies, and renal cell carcinomas1–3. Renal cell carcinomas constitute a particularly frequent cause of death in this disorder, occurring as bilateral and multifocal tumours, and presenting at an earlier age than in sporadic, non-familial cases of this tumour type. We report here that the VHL gene is linked to the locus encoding the human homologoue of theRAF1oncogene, which maps to chromosome 3p25 (ref. 4). Crossovers with the VHL locus suggest that the defect responsible for the VHL phenotype is not a mutation in theRAF1gene itself. An alternative or prior event to oncogene activation in tumour formation may be the inactivation of a putative 'tumour suppressor' which can be associated with both the inherited and sporadic forms of the cancer. Sporadic renal cell carcinomas have previously been associated with the loss of regions on chromosome 3p (refs 5, 6). Consequently, sporadic and VHL-associated forms of renal cell carcinoma might both result from alterations causing loss of function of the same 'tumour suppressor' gene on this chromosome.