Homozygous deletion scanning in hepatobiliary tumor cell lines reveals alternative pathways for liver carcinogenesis

Despite high rates of loss of heterozygosity affecting various chromosomes, the number of tumor suppressor genes (TSGs) found to be consistently involved in primary liver cancer is low. In the past decade, characterization of homozygous deletions (HDs) in tumors has become instrumental to identify n...

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Veröffentlicht in:Hepatology (Baltimore, Md.) Md.), 2003-04, Vol.37 (4), p.852-861
Hauptverfasser: Pineau, Pascal, Marchio, Agnès, Nagamori, Seishi, Seki, Shuichi, Tiollais, Pierre, Dejean, Anne
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container_title Hepatology (Baltimore, Md.)
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creator Pineau, Pascal
Marchio, Agnès
Nagamori, Seishi
Seki, Shuichi
Tiollais, Pierre
Dejean, Anne
description Despite high rates of loss of heterozygosity affecting various chromosomes, the number of tumor suppressor genes (TSGs) found to be consistently involved in primary liver cancer is low. In the past decade, characterization of homozygous deletions (HDs) in tumors has become instrumental to identify new TSGs or to reveal the influence of a particular TSG on the development of a specific tumor type. We performed a detailed HD profiling at 238 critical loci on a collection of 57 hepatobiliary tumor cell lines (hepatocellular, cholangiocellular, and bile duct carcinomas, hepatoblastomas, and immortalized hepatocytes). We identified HDs at 9 independent loci, the analysis of which was extended to 17 additional hepatobiliary tumor cell lines. In total, 34 homozygous losses involving 9 distinct genes were detected in the 74 cell lines analyzed. Besides expected deletions at the p16-INK4A/p14-ARF, FHIT, AXIN1, and p53 genes, we detected HDs at the PTEN, NF2, STK11, BAX, and LRPDIT genes that were formerly not known to be implicated in human liver tumorigenesis. In conclusion, our data suggest that these genes may represent novel liver tumor suppressive targets. Additional tumorigenic pathways should be carefully considered in hepatocarcinogenesis. (H epatology 2003;37:852-861.)
doi_str_mv 10.1053/jhep.2003.50138
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ispartof Hepatology (Baltimore, Md.), 2003-04, Vol.37 (4), p.852-861
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source MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects Bile Duct Neoplasms - genetics
Biochemistry, Molecular Biology
Biological and medical sciences
Cancer
Cell Cycle Proteins - genetics
Chromosome Mapping
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16 - genetics
Gastroenterology. Liver. Pancreas. Abdomen
Gene Deletion
Genes, p16
Genomics
Homozygote
Human health and pathology
Humans
Hépatology and Gastroenterology
Life Sciences
Liver Neoplasms - genetics
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical sciences
Tumor Cells, Cultured
Tumor Suppressor Protein p14ARF - genetics
Tumor Suppressor Proteins
Tumors
title Homozygous deletion scanning in hepatobiliary tumor cell lines reveals alternative pathways for liver carcinogenesis
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