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.

Polygenic control of hepatocarcinogenesis in Copenhagen x F344 rats / DE MIGLIO, Maria Rosaria; Pascale, Rosa Maria; Simile, Maria Maddalena; Muroni, Maria Rosaria; Virdis, P.; Kwong, K. M. T.; Wong, L. K. L.; Bosinco, G. M.; Pulina, F. R.; Calvisi, D. F.; Frau, M.; Wood, G. A.; Archer, M. C.; Feo, F.. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - 111:(2004), pp. 9-16. [10.1002/ijc.20225]

Polygenic control of hepatocarcinogenesis in Copenhagen x F344 rats

DE MIGLIO, Maria Rosaria;PASCALE, Rosa Maria;SIMILE, Maria Maddalena;MURONI, Maria Rosaria;Calvisi, D. F.;
2004-01-01

Abstract

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.
2004
Polygenic control of hepatocarcinogenesis in Copenhagen x F344 rats / DE MIGLIO, Maria Rosaria; Pascale, Rosa Maria; Simile, Maria Maddalena; Muroni, Maria Rosaria; Virdis, P.; Kwong, K. M. T.; Wong, L. K. L.; Bosinco, G. M.; Pulina, F. R.; Calvisi, D. F.; Frau, M.; Wood, G. A.; Archer, M. C.; Feo, F.. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - 111:(2004), pp. 9-16. [10.1002/ijc.20225]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/45353
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