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 |
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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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epatology 2003;37:852-861.)</description><subject>Bile Duct Neoplasms - genetics</subject><subject>Biochemistry, Molecular Biology</subject><subject>Biological and medical sciences</subject><subject>Cancer</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Chromosome Mapping</subject><subject>Cyclin-Dependent Kinase Inhibitor p15</subject><subject>Cyclin-Dependent Kinase Inhibitor p16 - genetics</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Deletion</subject><subject>Genes, p16</subject><subject>Genomics</subject><subject>Homozygote</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Hépatology and Gastroenterology</subject><subject>Life Sciences</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Medical sciences</subject><subject>Tumor Cells, Cultured</subject><subject>Tumor Suppressor Protein p14ARF - genetics</subject><subject>Tumor Suppressor Proteins</subject><subject>Tumors</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDFvGyEUgFHVqHGTzN0qlo7nPI7j7hijKK0rWWqHZkYcvLOJMFhwduT8-uLaqqeqExL6Ph7vI-QTgzkDwe9f1rid1wB8LoDx_h2ZMVF3FecC3pMZ1B1UknF5TT7m_AIAsqn7D-Sa1W3by66fkWkRN_HtsIq7TC16nFwMNBsdggsr6gItA_QUB-edTgc67TYxUYPeU-8CZppwj9pnqv2EKejJ7ZEWYf2qD5mOhfXlphg6GRfiCovj8i25GouEd-fzhjx_ffr1uKiWP759f3xYVkaIVlZ2NF1j9aCtxG7gRrYwStYPg20b3qI049gaqRvGh073fQO10QxasEIMwGvBb0h1enetvdomtykrqKidWjws1VbnCXdJQd130AjYs8Lfn3iTYs4Jx78SA3XsrY691bG3-tO7GJ9PxnY3bNBe-HPgAnw5A7pU9WPSwbh84ZqOd0IeOXniXp3Hw__mqsXTT8GAl48zeXGxtNw7TCobh8GgdQnNpGx0_1zgNwjOsKM</recordid><startdate>200304</startdate><enddate>200304</enddate><creator>Pineau, Pascal</creator><creator>Marchio, Agnès</creator><creator>Nagamori, Seishi</creator><creator>Seki, Shuichi</creator><creator>Tiollais, Pierre</creator><creator>Dejean, Anne</creator><general>Elsevier Inc</general><general>W.B. Saunders</general><general>Wiley</general><general>Wiley-Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0001-6541-5395</orcidid><orcidid>https://orcid.org/0000-0002-9407-1592</orcidid><orcidid>https://orcid.org/0000-0003-4778-6840</orcidid></search><sort><creationdate>200304</creationdate><title>Homozygous deletion scanning in hepatobiliary tumor cell lines reveals alternative pathways for liver carcinogenesis</title><author>Pineau, Pascal ; Marchio, Agnès ; Nagamori, Seishi ; Seki, Shuichi ; Tiollais, Pierre ; Dejean, Anne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5569-dfc74dabad9e7b3c960f918bbd6436e9cff6c9a413b7a88402ca1060d55b03253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Bile Duct Neoplasms - genetics</topic><topic>Biochemistry, Molecular Biology</topic><topic>Biological and medical sciences</topic><topic>Cancer</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Chromosome Mapping</topic><topic>Cyclin-Dependent Kinase Inhibitor p15</topic><topic>Cyclin-Dependent Kinase Inhibitor p16 - genetics</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Deletion</topic><topic>Genes, p16</topic><topic>Genomics</topic><topic>Homozygote</topic><topic>Human health and pathology</topic><topic>Humans</topic><topic>Hépatology and Gastroenterology</topic><topic>Life Sciences</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Medical sciences</topic><topic>Tumor Cells, Cultured</topic><topic>Tumor Suppressor Protein p14ARF - genetics</topic><topic>Tumor Suppressor Proteins</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pineau, Pascal</creatorcontrib><creatorcontrib>Marchio, Agnès</creatorcontrib><creatorcontrib>Nagamori, Seishi</creatorcontrib><creatorcontrib>Seki, Shuichi</creatorcontrib><creatorcontrib>Tiollais, Pierre</creatorcontrib><creatorcontrib>Dejean, Anne</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pineau, Pascal</au><au>Marchio, Agnès</au><au>Nagamori, Seishi</au><au>Seki, Shuichi</au><au>Tiollais, Pierre</au><au>Dejean, Anne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Homozygous deletion scanning in hepatobiliary tumor cell lines reveals alternative pathways for liver carcinogenesis</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2003-04</date><risdate>2003</risdate><volume>37</volume><issue>4</issue><spage>852</spage><epage>861</epage><pages>852-861</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><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. (H
epatology 2003;37:852-861.)</abstract><cop>Philadelphia, PA</cop><pub>Elsevier Inc</pub><pmid>12668978</pmid><doi>10.1053/jhep.2003.50138</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0001-6541-5395</orcidid><orcidid>https://orcid.org/0000-0002-9407-1592</orcidid><orcidid>https://orcid.org/0000-0003-4778-6840</orcidid></addata></record> |
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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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