H-ras Consensus Sequence and Mutations in Primary Hepatocellular Carcinomas of Lemurs and Lorises

• Published in: Veterinary pathology Vol. 48; no. 4; pp. 868 - 874
• Main Authors: Cullen, J. M., Williams, C., Zadrozny, L., Otstot, J. T., Solomon, G. G., Sills, R. C., Hong, H-H. L.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-07-2011
• Subjects: Animals; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - veterinary; Consensus Sequence; Female; Gene Expression Regulation, Neoplastic; Genes, ras - genetics; Lemur; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - veterinary; Loris; Lorisidae; Male; Mutation; Pan troglodytes; Primate Diseases - genetics; Primate Diseases - pathology; molecular biology; primate; zoo; liver; oncology; hepatocellular carcinoma
• ISSN: 0300-9858; 1544-2217
• DOI: 10.1177/0300985810388526

The authors have determined a consensus sequence for exons 1 and 2 of H-ras from captive lemurs and lorises and evaluated samples of nonneoplastic liver and hepatocellular carcinomas (HCC) from affected animals for mutations in these exons. Frozen liver samples were collected from 20 animals representing 9 different species with a sex distribution of 10 males and 10 females. A total of 26 liver samples, including 11 normal livers, 9 HCC, and 6 samples from nonneoplastic regions of liver from animals with HCC, were evaluated. This is the first report of the consensus sequence for exons 1 and 2 of H-ras in prosimians, and the authors have determined that it is identical to that of human H-ras and differs only slightly from the chimpanzee sequence. Point mutations were identified in 6 of the 9 HCC samples examined with codons 7, 22, 32, 56, 61, 84, and 96 affected. Two carcinomas had double mutations, and one tumor had triple mutations. One HCC had a mutation in codon 61, which is identical to a recognized affected codon for an H-ras “hot spot” in rodent neoplasia that has also been reported in human tumors. Although not statistically different, metastasis occurred in 5 of 6 HCC with H-ras mutation and only 1 of 3 HCC without mutations. There were 4 silent mutations that did not contain changes in the encoded amino acids, 2 of which were found in nonneoplastic regions of tumor-bearing liver.