1. Cancer Res. 2002 Aug 1;62(15):4459-63.
Chromosome mapping of multiple loci affecting the genetic predisposition to rat
liver carcinogenesis.
De Miglio MR(1), Pascale RM, Simile MM, Muroni MR, Calvisi DF, Virdis P, Bosinco
GM, Frau M, Seddaiu MA, Ladu S, Feo F.
Author information:
(1)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
hepatocarcinogenesis led 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.
PMID: 12154055 [PubMed - indexed for MEDLINE]
PUBMED: 12154055
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