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Yeung RS , Xiao GH , Jin F , Lee WC , Testa JR , Knudson AG
Predisposition to Renal-Carcinoma in the Eker Rat Is Determined by Germ-Line Mutation of the Tuberous-Sclerosis-2 (Tsc2) Gene
Proceedings of the National Academy of Sciences of the United States of America. 1994 Nov 22;91(24) :11413-11416
PMID: ISI:A1994PU28500027   
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Abstract
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.
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English Article PU285 PROC NAT ACAD SCI USA