{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T14:39:25Z","timestamp":1700663965783},"reference-count":14,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,2]],"date-time":"2009-01-02T00:00:00Z","timestamp":1230854400000},"content-version":"vor","delay-in-days":520,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2007,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Objectives\/Hypothesis:<\/jats:bold> Promoter hypermethylation of tumor suppressor genes is common in head and neck cancer as well as other primary cancers resulting in epigenetic gene silencing. Tissue inhibitor of metalloproteinase\u20103 (TIMP\u20103) has been shown to have promoter hypermethylation in several solid tumors, but has not been identified in head and neck squamous cell carcinoma (HNSCC). Our objective was to determine if TIMP\u20103 promoter was hypermethylated in HNSCC, if there was any correlation with death associated protein kinase (DAPK), a tumor suppressor whose promoter has been hypermethylated at high levels in HNSCC, and if any clinical factors influence hypermethylation of either of these genes.<\/jats:p><jats:p><jats:bold>Study Design:<\/jats:bold> Prospective study.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Tumor samples from 124 patients with HNSCC were evaluated for promoter hypermethylation for TIMP\u20103 and DAPK using quantitative methylation specific polymerase chain reaction (qMSP). We compared both TIMP\u20103 and DAPK hypermethylation in HNSCC with each other as well as with other clinical variables.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> We found that TIMP\u20103 was hypermethylated in approximately 71.8% of the tumor samples and DAPK was hypermethylated in 74.2%. The presence of TIMP\u20103 and DAPK promoter hypermethylation was significantly higher than in control specimens. More importantly, TIMP\u20103 and DAPK hypermethylations in these samples were highly correlated with a concordance of 78% (<jats:italic>P<\/jats:italic> &lt; .001). DAPK was also correlated with current alcohol consumption (<jats:italic>P<\/jats:italic> &lt; .028), but neither TIMP\u20103 nor DAPK hypermethylation was significantly correlated with other clinical variables or with survival.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> TIMP\u20103 promoter hypermethylation is elevated in HNSCC and is highly correlated with DAPK hypermethylation, implying a functional relationship between these genes.<\/jats:p>","DOI":"10.1097\/mlg.0b013e31806865a8","type":"journal-article","created":{"date-parts":[[2007,6,22]],"date-time":"2007-06-22T08:04:12Z","timestamp":1182499452000},"page":"1376-1380","source":"Crossref","is-referenced-by-count":17,"title":["Positive Correlation of Tissue Inhibitor of Metalloproteinase\u20103 and Death\u2010Associated Protein Kinase Hypermethylation in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.1002","volume":"117","author":[{"given":"Chetan S.","family":"Nayak","sequence":"first","affiliation":[]},{"given":"Andr\u00e9 Lopes","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Carmen","family":"Jeronimo","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[]},{"given":"Michael M.","family":"Kim","sequence":"additional","affiliation":[]},{"given":"Mohammad O.","family":"Hoque","sequence":"additional","affiliation":[]},{"given":"Steve","family":"Chang","sequence":"additional","affiliation":[]},{"given":"Wei\u2010Wen","family":"Jiang","sequence":"additional","affiliation":[]},{"given":"Wayne","family":"Koch","sequence":"additional","affiliation":[]},{"given":"William","family":"Westra","sequence":"additional","affiliation":[]},{"given":"David","family":"Sidransky","sequence":"additional","affiliation":[]},{"given":"Joseph","family":"Califano","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,1,2]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20740"},{"key":"e_1_2_6_3_2","first-page":"939","article-title":"Promoter hypermethylation patterns of p16, O6\u2010methylguanine\u2010DNA\u2010methyltransferase, and death\u2010associated protein kinase in tumors and saliva of head and neck cancer patients","volume":"61","author":"Rosas SL","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.130.1.39"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111507200"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.09.037"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:CLIN.0000037704.72028.72"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.132.6.668"},{"key":"e_1_2_6_9_2","first-page":"7694","article-title":"Death\u2010associated protein kinase promoter hypermethylation in normal human lymphocytes","volume":"63","author":"Reddy AN","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9821"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202588"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/excr.2000.5134"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/36599"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205528"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.02.003"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1097%2FMLG.0b013e31806865a8","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1097\/MLG.0b013e31806865a8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T13:19:50Z","timestamp":1699967990000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1097\/MLG.0b013e31806865a8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8]]},"references-count":14,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["10.1097\/MLG.0b013e31806865a8"],"URL":"https:\/\/doi.org\/10.1097\/mlg.0b013e31806865a8","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8]]}}}