PREDISPOSITION TO RENAL-CARCINOMA IN THE EKER RAT IS DETERMINED BY GERM-LINE MUTATION OF THE TUBEROUS-SCLEROSIS-2 (TSC2) GENE
PREDISPOSITION TO RENAL-CARCINOMA IN THE EKER RAT IS DETERMINED BY GERM-LINE MUTATION OF THE TUBEROUS-SCLEROSIS-2 (TSC2) GENE
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DOI：
10.1073/pnas.91.24.11413
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发表时间：
1994-11-22
影响因子：
11.1
通讯作者：
KNUDSON, AG
中科院分区：
文献类型：
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作者：
YEUNG, RS;XIAO, GH;KNUDSON, AG
肿瘤形成的遗传易感性通常涉及肿瘤抑制基因。Eker在大鼠中描述了一种遗传性肾癌模型。这些肿瘤与人类肾癌具有形态学相似性。连锁分析将该遗传突变定位于大鼠染色体10q12带。该区域与人类染色体带16p13.3同线，即结节性硬化症2（TSC 2）基因的位点。一个特定的重排的大鼠同源TSC2被发现cosegregate与承运人的易感突变。有或没有杂合性丢失的肿瘤仅表达突变等位基因，与两次打击假设一致。该突变产生了缺失3'端的异常转录物，该3'端通常含有与rap1GAP的催化结构域同源的区域。
Genetic predisposition to neoplasia often involves tumor suppressor genes. One such model of hereditary renal carcinoma was described in the rat by Eker. These tumors share morphologic similarities with human renal cancer. Linkage analysis localized the inherited mutation to rat chromosome band 10q12. This region is syntenic with human chromosome band 16p13.3, the site of the tuberous sclerosis 2 (TSC2) gene. A specific rearrangement of the rat homologue of TSC2 was found to cosegregate with carriers of the predisposing mutation. Tumors with or without loss of heterozygosity expressed only the mutant allele, consistent with the two-hit hypothesis. This mutation gave rise to an aberrant transcript that deletes the 3' end normally containing a region of homology with the catalytic domain of rap1GAP.