Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene.
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.
Division of Medical Science, Fox Chase Cancer Center, Philadelphia, PA 19111.
R S
RS
Yeung
G H
GH
Xiao
F
F
Jin
W C
WC
Lee
J R
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Testa
A G
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Knudson
D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D015321:Gene Rearrangement; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011922:Rats, Mutant Strains; D012097:Repressor Proteins / Q000235:genetics*; D014018:Tissue Distribution; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D017931:DNA Primers; D012333:RNA, Messenger; D012097:Repressor Proteins; C000624653:TSC2 protein, human; C000624655:Tsc2 protein, rat; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins