Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene.

RS Yeung, GH Xiao, F Jin, WC Lee… - Proceedings of the …, 1994 - National Acad Sciences
RS Yeung, GH Xiao, F Jin, WC Lee, JR Testa, AG Knudson
Proceedings of the National Academy of Sciences, 1994National Acad Sciences
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 …
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.
National Acad Sciences