RGD Reference Report - Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity. - Rat Genome Database

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Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity.

Authors: Tanuma, J  Hiai, H  Shisa, H  Hirano, M  Semba, I  Nagaoka, S  Kitano, M 
Citation: Tanuma J, etal., Int J Cancer 2002 Dec 20;102(6):638-42.
RGD ID: 631169
Pubmed: (View Article at PubMed) PMID:12448007
DOI: Full-text: DOI:10.1002/ijc.10751

Rats of the DA strain are highly susceptible to 4NQO-induced TCs, whereas WF rats are barely susceptible. In (DA x WF)F2 rats, 5 QTL, Tscc1-5, are responsible for most of the phenotypic variations, though they do not account for all of the phenotypic differences between WF and DA rats. Analysis of 40 tongue tumors >5 mm in diameter from (DA x WF)F1 rats for LOH at the Tscc loci revealed a high frequency of LOH in chromosomal regions where the Tscc2, -3 and -4 loci map. In most cases of LOH, the allele of the barely susceptible WF strain was lost, suggesting that these loci in the WF strain encode tumor-suppressor genes. Analysis of the same tumors for somatic mutations in oncogenes indicated frequent alteration of Ha-ras, which maps in the Tscc3 region, but rare mutation of the p15(INK4B) and p16(INK4A) genes or the p53 and Msh2 genes. Frequent LOH was also found on rat chromosomes 5 (RNO5) and 6 (RNO6). Tumors of large size accumulated LOH at multiple loci, suggesting the involvement of Tscc loci in tumor progression.

Disease Annotations    

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Tcas2  (Tongue tumor susceptibility QTL 2)
Tcas3  (Tongue tumor susceptibility QTL 3)
Tcas4  (Tongue tumor susceptibility QTL 4)

Objects referenced in this article
Strain DA DA Rattus norvegicus
Strain DA.WF-(D1Mgh21-D1Mgh10)(D4Mit11-Nos3)(D1Mit1-D1Mit3)/Kop null Rattus norvegicus
Strain DA.WF-(D4Mit11-Nos3)/Kop null Rattus norvegicus
Strain DA/Ham Dark-agouti Rattus norvegicus
Strain WF/Kga Wistar-Furth Rattus norvegicus

Additional Information