1. Int J Cancer. 2004 Aug 10;111(1):9-16.
Polygenic control of hepatocarcinogenesis in Copenhagen x F344 rats.
De Miglio MR(1), Pascale RM, Simile MM, Muroni MR, Virdis P, Kwong KM, Wong LK,
Bosinco GM, Pulina FR, Calvisi DF, Frau M, Wood GA, Archer MC, Feo F.
Author information:
(1)Division of Experimental Pathology and Oncology, Department of Biomedical
Sciences, University of Sassari, Sassari, Italy.
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.
Copyright 2004 Wiley-Liss, Inc.
PMID: 15185337 [PubMed - indexed for MEDLINE]
PUBMED: 15185337
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