{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T17:54:02Z","timestamp":1773251642081,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T00:00:00Z","timestamp":1580774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FDN\u2010143347"],"award-info":[{"award-number":["FDN\u2010143347"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:p>DNA methylation analysis may improve risk stratification in cervical screening. We used a pan\u2010epigenomic approach to identify new methylation markers along the continuum of cervical intraepithelial neoplasia (CIN) to cervical cancer. Physician\u2010collected samples (54 normal, 50 CIN1, 40 CIN2 and 42 CIN3) were randomly selected from women at a single\u2010center colposcopy clinic. Extracted DNA was subjected to Illumina Infinium EPIC array analysis, and methylation was assessed blinded to histopathological and clinical data. CpG sites whose state of methylation correlated with lesion grade were assessed (Spearman correlation), and a weighted methylation score was calculated comparing normal to CIN3. Validation of the top selected genes was performed in an independent cohort (100 normal, 50 CIN1, 50 CIN2, 50 CIN3 and 8 cervical cancers) of new patients, referred for colposcopic examination at three hospitals, using targeted DNA methylation Illumina amplicon sequencing. The relationship between a combined weighted marker score and progression from normal through precancerous lesions and cervical cancer was compared using one\u2010way ANOVA. Our analyses revealed 7,715 CpGs whose methylation level correlated with progression (from normal to CIN1, CIN2 and CIN3), with a significant trend of increased methylation with lesion grade. We shortlisted a bigenic (hyaluronan synthase 1, <jats:italic>HAS1<\/jats:italic> and ATPase phospholipid transporting 10A, <jats:italic>ATP10A<\/jats:italic> corresponding to cg03419058 and cg13944175 sites) marker set; <jats:italic>r<\/jats:italic> =\u20090.55, <jats:italic>p<\/jats:italic> &lt;\u20090.0001. Validation of the four most discriminating genes (<jats:italic>CA10<\/jats:italic>, <jats:italic>DPP10<\/jats:italic>, <jats:italic>FMN2<\/jats:italic> and <jats:italic>HAS1<\/jats:italic>) showed a significant correlation between methylation levels and disease progression (<jats:italic>p<\/jats:italic>\u2010value &lt;\u20092.2 \u00d7\u200910<jats:sup>\u221216<\/jats:sup>, adjusted <jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup> =\u20090.952). Translational research of the identified genes to future clinical applications is warranted.<\/jats:p>","DOI":"10.1002\/ijc.32880","type":"journal-article","created":{"date-parts":[[2020,1,26]],"date-time":"2020-01-26T03:20:10Z","timestamp":1580008810000},"page":"1264-1274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Genome\u2010wide DNA methylation profiling identifies two novel genes in cervical neoplasia"],"prefix":"10.1002","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-0370","authenticated-orcid":false,"given":"Mariam","family":"El\u2010Zein","sequence":"first","affiliation":[{"name":"Division of Cancer Epidemiology McGill University  Montr\u00e9al QC Canada"},{"name":"Gerald Bronfman Department of Oncology McGill University  Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Cheishvili","sequence":"additional","affiliation":[{"name":"Gerald Bronfman Department of Oncology McGill University  Montr\u00e9al QC Canada"},{"name":"HKG Epitherapeutics  Science Park Hong Kong"},{"name":"Montreal EpiTerapia Inc.  Montreal QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Gotlieb","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology and Colposcopy McGill University, Jewish General Hospital  Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Gynecologic Cancer Service McGill University Health Centre, Glen Site Cedars Cancer Centre  Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Hemmings","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology McGill University Health Centre \u2010 St Mary's Hospital Centre  Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel A.","family":"Behr","sequence":"additional","affiliation":[{"name":"Department of Medicine McGill University Health Centre  Montr\u00e9al QC Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moshe","family":"Szyf","sequence":"additional","affiliation":[{"name":"HKG Epitherapeutics  Science Park Hong Kong"},{"name":"Montreal EpiTerapia Inc.  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