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.
| Original language | English |
|---|---|
| Pages (from-to) | 11413-11416 |
| Number of pages | 4 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 91 |
| Issue number | 24 |
| DOIs | |
| State | Published - Nov 22 1994 |
Keywords
- Animals
- Base Sequence
- Carcinoma/genetics
- Chromosomes, Human, Pair 16
- DNA Primers/chemistry
- Gene Expression
- Gene Rearrangement
- Genes, Tumor Suppressor
- Genetic Linkage
- Humans
- Kidney Neoplasms/genetics
- Molecular Sequence Data
- Mutation
- RNA, Messenger/genetics
- Rats
- Rats, Mutant Strains
- Repressor Proteins/genetics
- Tissue Distribution
- Tuberous Sclerosis Complex 2 Protein
- Tuberous Sclerosis/genetics
- Tumor Suppressor Proteins
