Multiple Genetic Alterations, 4Q28, A New Suppressor... : Hepatology (original) (raw)
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Multiple Genetic Alterations, 4Q28, A New Suppressor Region, and Potential Gender Differences in Human Hepatocellular Carcinoma
Hammond, Christine1; Jeffers, Lennox2; Carr, Brian I.3; Simon, Daniela RNDr, MCP*,1
1_MCP & Hahnemann School of Medicine, FL;Pittsburgh, PA_
2_The University of Miami, Miami, FL; Pittsburgh, PA_
3_University of Pittsburgh, Pittsburgh, PA_
* Hahnemann School of Medicine, Department of Pathology and Laboratory Medicine, Broad & Vine, Philadelphia, PA 19102–1192. fax: 215–246–5918; E-mail: [email protected].
Received: 24 November 1998; Accepted: 24 February 1999
Abstract
Primary hepatocellular carcinomas (HCCs) of different etiologies were studied to determine the rate of alteration of several genetic regions previously associated with the HCC phenotype. The focus of our study was to identify the frequency of genetic alterations within individual HCCs and their distribution among male and female cases. Genetic differences were evaluated between DNA isolated from tumor (T) and corresponding non–tumor (N) tissue using short tandem repeat (STR)–microsatellites and restriction fragment length polymorphism (RFLP) analyses. Twenty–eight HCC cases were studied with polymorphic markers from different parts of the genome. Three or more loci were identified with genetic alterations from 28 loci tested in 63% of HCC cases. The highest frequency of alteration occurred in the chromosome regions 1p36, 13q14, 17p13, and the 4q28 region identified in HCCs for the first time. High loss of heterozygosity (LOH) in 1p36, 4q28, 13q14, and 17p13 regions indicates important HCC suppressors within the regions. The study documents no association between cause and specific genetic change or their frequency in HCCs analyzed. The data document a significant gender distortion for genetic alteration in chromosome 13q14 and 17p13 regions and a concordant gender alteration rate in the 1p36 and 4q28 regions. An overall higher frequency of genetic alterations was identified in male cases. Future study with an extended number of HCC cases should substantiate the frequency of alteration between genders and identify tentative suppressors in the 1p36 and 4q28 regions.
Copyright © 1999 American Association for the Study of Liver Diseases.