This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by De Miglio, M. R. Articles by Feo, F. Search for Related Content PubMed PubMed Citation Articles by De Miglio, M. R. Articles by Feo, F.

Chromosome Mapping of Multiple Loci Affecting the Genetic Predisposition to Rat Liver Carcinogenesis¹

Department of Biomedical Sciences, Division of Experimental Pathology and Oncology, University of Sassari, 07100 Sassari, Italy

Previous studies on (BNxF344)F1 (BFF1) rat model of genetic predisposition to hepatocarcinogenesisled to the identification, in BFF1xF344 backcross progeny, of two hepatocarcinogenesis susceptibility (Hcs) and three resistance (Hcr) loci affecting the progression of neoplastic liver nodules. To evaluate the presence of other hepatocarcinogenesis-related loci in the BFF1 genome, nodule induction by resistant hepatocyte model in 116 male BFF2 rats 32 weeks after initiation with diethylnitrosamine was subjected to quantitative trait loci analysis. The rats were typed with 179 genetic markers, and linkage analysis identified three loci on chromosomes 1, 16, and 6, in significant linkage with nodule mean volume (V), volume fraction, and number, respectively, and two loci on chromosomes 4 and 8 in suggestive linkage with V. These loci were differently positioned with respect to Hcs and Hcr loci mapped previously in backcross rats. On the basis of phenotypic and allele distribution patterns of BFF2 rats, loci on chromosomes 1 and 16 were identified as Hcs3 and Hcs4, and loci on chromosomes 4, 8, and 6 as Hcr4, Hcr5, and Hcr6. Additive interactions occurred between Hcs3 and Hcs4, and Hcr4 and a locus on chromosome 3 with less than suggestive linkage with V. All of the loci were in chromosomal regions syntenic to mouse and/or human chromosomal segments showing allelic gain or loss in hepatocellular carcinomas. These data indicate that inheritance of predisposition to rat liver tumor is characterized by the interplay of several genetic factors and suggest some possible mechanisms of polygenic control of human liver cancer.

This article has been cited by other articles:

				F. Feo, M. Frau, M. L. Tomasi, S. Brozzetti, and R. M. Pascale Genetic and Epigenetic Control of Molecular Alterations in Hepatocellular Carcinoma Experimental Biology and Medicine, July 1, 2009; 234(7): 726 - 736. [Abstract] [Full Text] [PDF]

				M. R. De Miglio, P. Virdis, D. F. Calvisi, D. Mele, M. R. Muroni, M. Frau, F. Pinna, M. L. Tomasi, M. M. Simile, R. M. Pascale, et al. Identification and chromosome mapping of loci predisposing to colorectal cancer that control Wnt/{beta}-catenin pathway and progression of early lesions in the rat Carcinogenesis, November 1, 2007; 28(11): 2367 - 2374. [Abstract] [Full Text] [PDF]

				M. R. De Miglio, P. Virdis, D. F. Calvisi, M. Frau, M. R. Muroni, M. M. Simile, L. Daino, G. M. Careddu, E. Sanna-Passino, R. M. Pascale, et al. Mapping a Sex Hormone-Sensitive Gene Determining Female Resistance to Liver Carcinogenesis in a Congenic F344.BN-Hcs4 Rat Cancer Res., November 1, 2006; 66(21): 10384 - 10390. [Abstract] [Full Text] [PDF]

				J. Lazar, C. Moreno, H. J. Jacob, and A. E. Kwitek Impact of genomics on research in the rat Genome Res., December 1, 2005; 15(12): 1717 - 1728. [Abstract] [Full Text] [PDF]

				M. M. Simile, G. Pagnan, F. Pastorino, C. Brignole, M. R. De Miglio, M. R. Muroni, G. Asara, M. Frau, M. A. Seddaiu, D. F. Calvisi, et al. Chemopreventive N-(4-hydroxyphenyl)retinamide (fenretinide) targets deregulated NF-{kappa}B and Mat1A genes in the early stages of rat liver carcinogenesis Carcinogenesis, February 1, 2005; 26(2): 417 - 427. [Abstract] [Full Text] [PDF]

				T.-T. Li, S. Larrucea, S. Souza, S. M. Leal, J. A. Lopez, E. M. Rubin, B. Nieswandt, and P. F. Bray Genetic variation responsible for mouse strain differences in integrin {alpha}2 expression is associated with altered platelet responses to collagen Blood, May 1, 2004; 103(9): 3396 - 3402. [Abstract] [Full Text] [PDF]

				F.S. Falvella, R. M. Pascale, M. Gariboldi, G. Manenti, M. R. De Miglio, M. M. Simile, T. A. Dragani, and F. Feo Stearoyl-CoA desaturase 1 (Scd1) gene overexpression is associated with genetic predisposition to hepatocarcinogenesis in mice and rats Carcinogenesis, November 1, 2002; 23(11): 1933 - 1936. [Abstract] [Full Text] [PDF]