Liver, Pancreas, and Biliary TractGenetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis*,**
Section snippets
Patients and samples
Primary hepatocellular carcinoma and matched nontumor liver tissues were obtained from 137 patients during hepatectomy (n = 109), liver transplantation (n = 26), or at autopsy (n = 2) in 4 French surgical departments from 1992 to 1998. Fibrolamellar carcinomas were excluded from the series. Tumor tissue samples were dissected and nontumor tissues (>50 mg) were taken as far from the tumor as possible. Tissues were stored at −80°C until DNA extraction using the Qiaquick extraction kit (Qiagen,
Allelotyping results
A total of 335 microsatellite markers distributed among the 39 autosomal chromosome arms were characterized for each tumor and matched nontumor DNAs. More than 70% of the loci were informative per individual, and the status of more than 99.5% of the chromosome arms have been defined as conserved or deleted in the tumor. To avoid artifactual results, for all cases, the LOH status of a chromosome arm was attributed if at least 2 adjacent markers showed LOH. In all cases, more than 99% of the
Discussion
This study provides an exhaustive analysis of the relations that exist between the genetic alterations frequently found in HCC and the histoclinical characteristics of the tumors. For the first time, search for LOH on all chromosome arms and for mutations in 3 genes, P53, β-catenin, and Axin1, were carried out on the same series of tumors. Because the previously published series have investigated only a specific subset of genetic alterations, the correlations existing between all the different
Acknowledgements
The authors thank Dr. Leigh Pascoe for helpful discussions and critical reading of the manuscript; Prof. Jean-François Flejou, Prof. Frédérique Capron, and Prof. Balabaud for providing tumor samples; Jean-Christophe Beaudoin, Damien Gerald, Christelle Vaury, Catherine Massart, Richard Hamelin, and Jan Bayer for help in the LOH, mutation, and flow cytometry screening; Jean-Michel Pawlotsky for providing HBV reference serum; and Gavin Sherlock for his kind gift of cluster software for the
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Cited by (0)
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Address requests for reprints to: Jessica Zucman, M.D., Ph.D., INSERM U434, Laboratoire de Génétique des tumeurs, Centre d'étude du polymorphisme humain, 27 rue Juliette Dodu, 75010 Paris, France. e-mail: [email protected]; fax: (33) 15-372-5158.
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Supported by the Association de la Recherche sur le Cancer (grant no. 9382), the Ligue départementale de Lutte Contre le Cancer de la Dordogne, and the INSERM.