Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck
Tumor suppressor genes play an important role in normal growth regulation. Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possi...
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Veröffentlicht in: | Genes chromosomes & cancer 1998-04, Vol.21 (4), p.333-339 |
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creator | Pearlstein, Richard P. Benninger, Michael S. Carey, Thomas E. Zarbo, Richard J. Torres, Frank X. Rybicki, Benjamin A. Van Dyke, Daniel L. |
description | Tumor suppressor genes play an important role in normal growth regulation. Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possible marker of progression in head and neck squamous cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA were extracted from fresh tissue and paraffin blocks and were amplified by PCR using primers for three microsatellite repeat polymorphisms in 18q (D18S336, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two‐year survival compared to those without 18q LOH (30% vs. 63%; P=0.008). In a Cox proportional hazards model in which time from diagnosis to death was the outcome variable, patients with 18q LOH had an unadjusted relative risk (RR) of death of 2.46 (P = 0.005). When 18q LOH was placed in a multivariate model controlling for possible confounders in the study, the RR for death was still elevated (RR = 2.10; P = 0.025). The observation of a prognostic association between 18q LOH and poor patient survival suggests that loss of an 18q tumor suppressor gene or genes is important in the progression of HNSCC. Genes Chromosomes Cancer 21:333–339, 1998. © 1998 Wiley‐Liss, Inc. |
doi_str_mv | 10.1002/(SICI)1098-2264(199804)21:4<333::AID-GCC7>3.0.CO;2-# |
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Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possible marker of progression in head and neck squamous cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA were extracted from fresh tissue and paraffin blocks and were amplified by PCR using primers for three microsatellite repeat polymorphisms in 18q (D18S336, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two‐year survival compared to those without 18q LOH (30% vs. 63%; P=0.008). In a Cox proportional hazards model in which time from diagnosis to death was the outcome variable, patients with 18q LOH had an unadjusted relative risk (RR) of death of 2.46 (P = 0.005). When 18q LOH was placed in a multivariate model controlling for possible confounders in the study, the RR for death was still elevated (RR = 2.10; P = 0.025). The observation of a prognostic association between 18q LOH and poor patient survival suggests that loss of an 18q tumor suppressor gene or genes is important in the progression of HNSCC. Genes Chromosomes Cancer 21:333–339, 1998. © 1998 Wiley‐Liss, Inc.</description><identifier>ISSN: 1045-2257</identifier><identifier>EISSN: 1098-2264</identifier><identifier>DOI: 10.1002/(SICI)1098-2264(199804)21:4<333::AID-GCC7>3.0.CO;2-#</identifier><identifier>PMID: 9559345</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Carcinoma, Squamous Cell - genetics ; Chromosome Deletion ; Chromosomes, Human, Pair 18 - genetics ; Female ; Head and Neck Neoplasms - genetics ; Humans ; Loss of Heterozygosity ; Male ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Survival Analysis</subject><ispartof>Genes chromosomes & cancer, 1998-04, Vol.21 (4), p.333-339</ispartof><rights>Copyright © 1998 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c3267-e7a955c83cb1a171955c240c03b8464e264839f4e4e2c6f8453b3ebce483112b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2F%28SICI%291098-2264%28199804%2921%3A4%3C333%3A%3AAID-GCC7%3E3.0.CO%3B2-%23$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2F%28SICI%291098-2264%28199804%2921%3A4%3C333%3A%3AAID-GCC7%3E3.0.CO%3B2-%23$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9559345$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pearlstein, Richard P.</creatorcontrib><creatorcontrib>Benninger, Michael S.</creatorcontrib><creatorcontrib>Carey, Thomas E.</creatorcontrib><creatorcontrib>Zarbo, Richard J.</creatorcontrib><creatorcontrib>Torres, Frank X.</creatorcontrib><creatorcontrib>Rybicki, Benjamin A.</creatorcontrib><creatorcontrib>Van Dyke, Daniel L.</creatorcontrib><title>Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck</title><title>Genes chromosomes & cancer</title><addtitle>Genes Chromosom. Cancer</addtitle><description>Tumor suppressor genes play an important role in normal growth regulation. Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possible marker of progression in head and neck squamous cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA were extracted from fresh tissue and paraffin blocks and were amplified by PCR using primers for three microsatellite repeat polymorphisms in 18q (D18S336, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two‐year survival compared to those without 18q LOH (30% vs. 63%; P=0.008). In a Cox proportional hazards model in which time from diagnosis to death was the outcome variable, patients with 18q LOH had an unadjusted relative risk (RR) of death of 2.46 (P = 0.005). When 18q LOH was placed in a multivariate model controlling for possible confounders in the study, the RR for death was still elevated (RR = 2.10; P = 0.025). The observation of a prognostic association between 18q LOH and poor patient survival suggests that loss of an 18q tumor suppressor gene or genes is important in the progression of HNSCC. Genes Chromosomes Cancer 21:333–339, 1998. © 1998 Wiley‐Liss, Inc.</description><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Chromosome Deletion</subject><subject>Chromosomes, Human, Pair 18 - genetics</subject><subject>Female</subject><subject>Head and Neck Neoplasms - genetics</subject><subject>Humans</subject><subject>Loss of Heterozygosity</subject><subject>Male</subject><subject>Multivariate Analysis</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Survival Analysis</subject><issn>1045-2257</issn><issn>1098-2264</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkNluEzEUhkcIVErhEZAsIaH2YoK3WRwqpGpKQ1BEpLaAxM3B43gUt7PFnuny9tgkChe94Mpn8_-f80XRKcETgjH9cHw1L-YnBIs8pjTlx0SIHPMTSqb8lDE2nZ7Nz-NZUWSf2ARPiuVHGr97Fh3uPzwPMU98nGQvo1fO3WCMUyaSg-hAJIlgPDmMfi8651BXIZJvUG_1yqjBob7rLHKjvTN3sg7dXg5Gt75zb4Y1cptRNt3okNJ1jZS0yrRdI8PgsNZoreUKyXaFWq1uX0cvKlk7_Wb3HkXfLz5fF1_ixXI2L84WsWI0zWKdSb-TypkqiSQZCQnlWGFW5jzl2t-TM1Fx7UOVVjlPWMl0qbQvE0JLdhS93-r2ttuM2g3QGBf2k632q0ImckKFwH7wcjuorD_d6gp6axppH4FgCOABAngIHCFwhC14oAQ4ePAAHjwE8MAAQ7EE6kXf7tzHstGrveSO8z_Te1PrxyeO_zF84vc386LxVtS4QT_sRaW9hTRjWQI_v83gCv-4vvz66xwW7A_Hj6pT</recordid><startdate>199804</startdate><enddate>199804</enddate><creator>Pearlstein, Richard P.</creator><creator>Benninger, Michael S.</creator><creator>Carey, Thomas E.</creator><creator>Zarbo, Richard J.</creator><creator>Torres, Frank X.</creator><creator>Rybicki, Benjamin A.</creator><creator>Van Dyke, Daniel L.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</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>7X8</scope></search><sort><creationdate>199804</creationdate><title>Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck</title><author>Pearlstein, Richard P. ; Benninger, Michael S. ; Carey, Thomas E. ; Zarbo, Richard J. ; Torres, Frank X. ; Rybicki, Benjamin A. ; Van Dyke, Daniel L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3267-e7a955c83cb1a171955c240c03b8464e264839f4e4e2c6f8453b3ebce483112b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Chromosome Deletion</topic><topic>Chromosomes, Human, Pair 18 - genetics</topic><topic>Female</topic><topic>Head and Neck Neoplasms - genetics</topic><topic>Humans</topic><topic>Loss of Heterozygosity</topic><topic>Male</topic><topic>Multivariate Analysis</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Survival Analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pearlstein, Richard P.</creatorcontrib><creatorcontrib>Benninger, Michael S.</creatorcontrib><creatorcontrib>Carey, Thomas E.</creatorcontrib><creatorcontrib>Zarbo, Richard J.</creatorcontrib><creatorcontrib>Torres, Frank X.</creatorcontrib><creatorcontrib>Rybicki, Benjamin A.</creatorcontrib><creatorcontrib>Van Dyke, Daniel L.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Genes chromosomes & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pearlstein, Richard P.</au><au>Benninger, Michael S.</au><au>Carey, Thomas E.</au><au>Zarbo, Richard J.</au><au>Torres, Frank X.</au><au>Rybicki, Benjamin A.</au><au>Van Dyke, Daniel L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck</atitle><jtitle>Genes chromosomes & cancer</jtitle><addtitle>Genes Chromosom. Cancer</addtitle><date>1998-04</date><risdate>1998</risdate><volume>21</volume><issue>4</issue><spage>333</spage><epage>339</epage><pages>333-339</pages><issn>1045-2257</issn><eissn>1098-2264</eissn><abstract>Tumor suppressor genes play an important role in normal growth regulation. Loss or inactivation of these genes has been implicated in the development of squamous cell cancer and progression of neoplasia. Previous studies in our laboratories have implicated chromosome 18 long‐arm deletions as a possible marker of progression in head and neck squamous cell cancer (HNSCC). To test this hypothesis, we evaluated DNA from 67 HNSCC patients for loss of heterozygosity (LOH) at 18q loci, and for association of LOH with survival. Tumor and normal DNA were extracted from fresh tissue and paraffin blocks and were amplified by PCR using primers for three microsatellite repeat polymorphisms in 18q (D18S336, D18S34, and MBP). A total of 27 (40%) patients had LOH of 18q, and these patients had a statistically significantly poorer two‐year survival compared to those without 18q LOH (30% vs. 63%; P=0.008). In a Cox proportional hazards model in which time from diagnosis to death was the outcome variable, patients with 18q LOH had an unadjusted relative risk (RR) of death of 2.46 (P = 0.005). When 18q LOH was placed in a multivariate model controlling for possible confounders in the study, the RR for death was still elevated (RR = 2.10; P = 0.025). The observation of a prognostic association between 18q LOH and poor patient survival suggests that loss of an 18q tumor suppressor gene or genes is important in the progression of HNSCC. Genes Chromosomes Cancer 21:333–339, 1998. © 1998 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>9559345</pmid><doi>10.1002/(SICI)1098-2264(199804)21:4<333::AID-GCC7>3.0.CO;2-#</doi><tpages>7</tpages></addata></record> |
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subjects | Carcinoma, Squamous Cell - genetics Chromosome Deletion Chromosomes, Human, Pair 18 - genetics Female Head and Neck Neoplasms - genetics Humans Loss of Heterozygosity Male Multivariate Analysis Prognosis Proportional Hazards Models Survival Analysis |
title | Loss of 18q predicts poor survival of patients with squamous cell carcinoma of the head and neck |
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