{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T14:06:49Z","timestamp":1779026809784,"version":"3.51.4"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T00:00:00Z","timestamp":1484784000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T00:00:00Z","timestamp":1484784000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE023941"],"award-info":[{"award-number":["DE023941"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA131648"],"award-info":[{"award-number":["CA131648"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA115243"],"award-info":[{"award-number":["CA115243"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA097190"],"award-info":[{"award-number":["CA097190"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["CA047904"],"award-info":[{"award-number":["CA047904"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF\/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF\/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT\u2010PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank\u2010sum,\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank\u2010sum test\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF\/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05\u20130.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC.\n                  <\/jats:p>","DOI":"10.1002\/cam4.961","type":"journal-article","created":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T00:08:45Z","timestamp":1484784525000},"page":"397-407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma"],"prefix":"10.1002","volume":"6","author":[{"given":"Miriam M.","family":"Ben\u2010Dayan","sequence":"first","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine Montefiore Medical Center  Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Ow","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine Montefiore Medical Center  Bronx New York"},{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Albert Einstein College of Medicine Montefiore Medical Center  Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Belbin","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine Montefiore Medical Center  Bronx New York"},{"name":"Dicipline of Oncology Faculty of Medicine Memorial University of Newfoundland  St. John's Newfoundland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua","family":"Wetzler","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine Montefiore Medical Center  Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard V.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Albert Einstein College of Medicine Montefiore Medical Center  Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Childs","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine Montefiore Medical Center  Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenda","family":"Diergaarde","sequence":"additional","affiliation":[{"name":"Department of Epidemiology University of Pittsburgh Cancer Institute  Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. Neil","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\/Head and Neck Cancer Surgery University of North Carolina  Chapel Hill North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer R.","family":"Grandis","sequence":"additional","affiliation":[{"name":"Departments of Otolaryngology Head and Neck Surgery University of California San Francisco  California"},{"name":"Department of Clinical and Translational Science Institute University of California  San Francisco California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Prystowsky","sequence":"additional","affiliation":[{"name":"Department of Pathology Albert Einstein College of Medicine Montefiore Medical Center  Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolas F.","family":"Schlecht","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology &amp; Population Health and Medicine Albert Einstein College of Medicine  Bronx New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21332"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.129.1.44"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa032646"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912217"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv403"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.374"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/35096061"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28876"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200212000-00002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14129"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-3280"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-4-546"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.11.103"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-98141-3"},{"key":"e_1_2_7_16_1","volume-title":"TNM classification of malignant tumours","author":"Sobin L.","year":"2009"},{"key":"e_1_2_7_17_1","volume-title":"American Joint Committee on Cancer Staging Manual","author":"S. 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