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Polygenic control of hepatocarcinogenesis in Copenhagen × F344 rats

De Miglio, Maria Rosaria and Pascale, Rosa Maria and Simile, Maria Maddalena and Muroni, Maria Rosaria and Virdis, Patrizia and Kwong, Kelvin M.-T. and Wong, Leslie K.L. and Bosinco, Giovanni M. and Pulina, Franca Rossana and Calvisi, Diego Francesco and Frau, Maddalena and Wood, Geoffrey A. and Archer, Michael C. and Feo, Francesco (2004) Polygenic control of hepatocarcinogenesis in Copenhagen × F344 rats. International Journal of Cancer, Vol. 111 (1), p. 9-16. eISSN 1097-0215. Article.

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DOI: 10.1002/ijc.20225


Cop and CFF1 rats exhibit resistance to hepatocarcinogenesis, associated with high rates of remodeling of neoplastic lesions. We have mapped hepatocarcinogenesis susceptibility, resistance and remodeling loci affecting the number, volume and volume fraction of neoplastic nodules induced by the resistant hepatocyte model in male CFF2 rats. Three loci in significant linkage with the number or volume of nonremodeling lesions were identified on chromosomes 1, 4 and 18. Suggestive linkage with number or volume fraction of total, nonremodeling or remodeling lesions was found for 7 loci on chromosomes 1, 2, 13, 14 and 15. All of these loci showed significant allele-specific effects on the phenotypic traits. We also detected by analysis of variance 19 2-way interactions inducing phenotypic effects not predictable on the basis of the sum of separate effects. These novel epistatic loci were in significant linkage with the number and/or volume of total, nonremodeling or remodeling nodules. These data indicate that susceptibility to hepatocarcinogenesis in Cop rats is controlled by a complex array of genes with several gene-gene interactions and that different genetic mechanisms control remodeling and nonremodeling liver nodules. Frequent deregulation in human liver cancer of genes positioned in chromosomal segments syntenic to rat susceptibility/resistance loci suggests some similarities between the genetic mechanisms involved in hepatocarcinogenesis in rats and humans.

Item Type:Article
ID Code:1260
Uncontrolled Keywords:Phenotypic reversion, genetic susceptibility, hepatocarcinogenesis, neoplastic nodule, linkage mapping, epistatic interaction
Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Additional Information:Pubblicato online il 31 marzo 2004.
Deposited On:18 Aug 2009 10:04

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