{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:45:37Z","timestamp":1789659937972,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T00:00:00Z","timestamp":1430265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Grants Council Area of Excellence (AoE) Hong Kong","award":["AoE\/M-06\/08"],"award-info":[{"award-number":["AoE\/M-06\/08"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Altered patterns of <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation are key features of cancer. Nasopharyngeal carcinoma (<jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>; however, genome\u2010wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> tumors and nontumor counterparts using a high\u2010throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (<jats:styled-content style=\"fixed-case\">TCGA<\/jats:styled-content>). In <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>, the hypermethylation pattern was more dominant than hypomethylation and the majority of <jats:italic>de novo<\/jats:italic> methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> (false discovery rate; <jats:styled-content style=\"fixed-case\">FDR<\/jats:styled-content>=1.33\u00a0\u00d7\u00a010<jats:sup>\u22129<\/jats:sup>), but was less obvious in other types of solid tumors except for prostate and Epstein\u2013Barr virus (<jats:styled-content style=\"fixed-case\">EBV<\/jats:styled-content>)\u2010positive gastric cancer (<jats:styled-content style=\"fixed-case\">FDR<\/jats:styled-content>&lt;10<jats:sup>\u22123<\/jats:sup>). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation and histone modification function together, leading to epigenetic deregulation in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>. Our study highlights the importance of epigenetic deregulation in <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content>. Polycomb Complex 2 (<jats:styled-content style=\"fixed-case\">PRC<\/jats:styled-content>2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for <jats:styled-content style=\"fixed-case\">NPC<\/jats:styled-content> detection.<\/jats:p>","DOI":"10.1002\/cam4.451","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T05:21:00Z","timestamp":1430371260000},"page":"1079-1090","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma"],"prefix":"10.1002","volume":"4","author":[{"given":"Wei","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology University of Hong Kong Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur Kwok Leung","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology University of Hong Kong Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine Mun Yee","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology University of Hong Kong Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology University of Hong Kong Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology University of Hong Kong Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger Kai Cheong","family":"Ngan","sequence":"additional","affiliation":[{"name":"Center for Nasopharyngeal Carcinoma Research University of Hong Kong Hong Kong (SAR) China"},{"name":"Department of Clinical Oncology Queen Elizabeth Hospital Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Tong","family":"Ng","sequence":"additional","affiliation":[{"name":"Center for Nasopharyngeal Carcinoma Research University of Hong Kong Hong Kong (SAR) China"},{"name":"Department of Clinical Oncology Pamela Youde Nethersole Eastern Hospital Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Wing Mui","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Nasopharyngeal Carcinoma Research University of Hong Kong Hong Kong (SAR) China"},{"name":"Department of Clinical Oncology University of Hong Kong\u2010Shenzhen Hospital Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun Chung","family":"Yau","sequence":"additional","affiliation":[{"name":"Center for Nasopharyngeal Carcinoma Research University of Hong Kong Hong Kong (SAR) China"},{"name":"Department of Oncology Princess Margaret Hospital Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Ho Fu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology University of Hong Kong Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Li","family":"Lung","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology University of Hong Kong Hong Kong (SAR) China"},{"name":"Center for Nasopharyngeal Carcinoma Research University of Hong Kong Hong Kong (SAR) China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.471"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07107"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1598"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1719"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2012.01.007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66698-6"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1452"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.07.007"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003103"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208812"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900198106"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29192"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.20079"},{"key":"e_1_2_7_15_1","first-page":"131","article-title":"Promoter hypermethylation of multiple genes in nasopharyngeal carcinoma","volume":"8","author":"Kwong J.","year":"2002","journal-title":"Clin. 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