Frequent loss of heterozygosity at the Hcr1 (hepatocarcinogenesis resistance) locus on chromosome 10 in primary hepatocellular carcinomas from LFF1 rat strain

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
M R De MiglioF Feo

Abstract

Hepatocarcinogenesis sensitivity (Hcs1, 2) and resistance (Hcr1-3) loci have been identified by linkage analysis on rat chromosomes 7 and 1, and 10, 4, and 8, respectively. Cytogenetic studies documented deletions on chromosomes 3 and 6 of neoplastic rat hepatocytes. Hepatocellular carcinomas (HCCs) were produced in F1 hybrid rats between Long-Evans (LE) and Fisher 344 (F344) rats. Scanning of the above chromosomes for loss of heterozygosity (LOH) showed allelic imbalance (AI) at multiple regions on chromosomes 6, 7, and 10q. Detailed deletion mapping of chromosome 10 localized a putative suppressor Hcr1 gene to within a 3.2-cM interval flanked by D10Rat51 and D10Rat121. Two other distinct regions with frequent AIs were found inside the Hcr1 locus, at marker loci including DNaseI and Mrp genes, and in a segment including 4 consecutive markers (D10Rat64, D10Rat182, D10Rat113, D10Rat216). In 40% of HCCs, AI was seen at the p53 locus. AI on chromosome 7 occurred at the Hcs1 locus, where is located c-myc, which is amplified in HCCs, suggesting allelic gain. Most AIs occurred in poorly/moderately differentiated carcinomas, and a few events were seen in well-differentiated tumors on chromosomes 7 and 10. These data suggest that alter...Continue Reading

Citations

Jul 10, 2003·Biochimica Et Biophysica Acta·Yan FuToshihiro Sugiyama
May 25, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Rosa M PascaleFrancesco Feo
Feb 24, 2010·Molecular Aspects of Medicine·Maddalena FrauRosa M Pascale
Aug 13, 2008·International Journal of Cancer. Journal International Du Cancer·Diego F CalvisiRosa M Pascale
May 27, 2016·Cancer Medicine·Jiliang ShenXiujun Cai
Dec 27, 2003·World Journal of Gastroenterology : WJG·Wei-Guo DengToshihiro Sugiyama
Oct 2, 2019·Cancers·Rosa M PascaleDiego F Calvisi

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