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

Abstract : 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-02870450
Contributor : Pascal Pineau <>
Submitted on : Tuesday, June 16, 2020 - 4:52:54 PM
Last modification on : Thursday, July 2, 2020 - 11:36:20 AM

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Pascal Pineau, Agnès Marchio, Seishi Nagamori, Shuichi Seki, Pierre Tiollais, et al.. Homozygous deletion scanning in hepatobiliary tumor cell lines reveals alternative pathways for liver carcinogenesis. Hepatology, Wiley-Blackwell, 2003, 37 (4), pp.852-861. ⟨10.1053/jhep.2003.50138⟩. ⟨pasteur-02870450⟩

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