{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:15:29Z","timestamp":1781835329130,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,11,24]],"date-time":"2014-11-24T00:00:00Z","timestamp":1416787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C8216\/A11963"],"award-info":[{"award-number":["C8216\/A11963"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C588\/A4994"],"award-info":[{"award-number":["C588\/A4994"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C588\/A10589"],"award-info":[{"award-number":["C588\/A10589"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004431","name":"European Commission Directorate-General for Research and Innovation","doi-asserted-by":"publisher","award":["CHEMORES, LSHC CT-2007-037665"],"award-info":[{"award-number":["CHEMORES, LSHC CT-2007-037665"]}],"id":[{"id":"10.13039\/100004431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bramall Fellowship and a Medical Council Clinical Training Fellowship","award":["G0802123"],"award-info":[{"award-number":["G0802123"]}]},{"name":"Radiumhemmet Research Funds","award":["101152"],"award-info":[{"award-number":["101152"]}]},{"name":"Radiumhemmet Research Funds","award":["124092"],"award-info":[{"award-number":["124092"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2015,6,15]]},"abstract":"<jats:p>To investigate the predictive and prognostic value of O<jats:sup>6<\/jats:sup>\u2010methylguanine DNA methyltransferase (<jats:italic>MGMT<\/jats:italic>) inactivation by analyses of promoter methylation in pretreatment tumor biopsies from patients with cutaneous melanoma treated with dacarbazine (DTIC) or temozolomide (TMZ) were performed. The patient cohorts consisted of Belgian and Swedish disseminated melanoma patients. Patients were subdivided into those receiving single\u2010agent treatment with DTIC\/TMZ (cohort S, <jats:italic>n<\/jats:italic>\u2009=\u200974) and those treated with combination chemotherapy including DTIC\/TMZ (cohort C, <jats:italic>n<\/jats:italic>\u2009=\u200979). Median follow\u2010up was 248 and 336 days for cohort S and cohort C, respectively. <jats:italic>MGMT<\/jats:italic> promoter methylation was assessed by three methods. The methylation\u2010related transcriptional silencing of <jats:italic>MGMT<\/jats:italic> mRNA expression was assessed by real\u2010time RT\u2010PCR. Response to chemotherapy and progression\u2010free survival (PFS) and overall survival were correlated to <jats:italic>MGMT<\/jats:italic> promoter methylation status. <jats:italic>MGMT<\/jats:italic> promoter methylation was detected in tumor biopsies from 21.5 % of the patients. <jats:italic>MGMT<\/jats:italic> mRNA was found to be significantly lower in tumors positive for <jats:italic>MGMT<\/jats:italic> promoter methylation compared to tumors without methylation in both treatment cohorts (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005). DTIC\/TMZ therapy response rate was found to be significantly associated with <jats:italic>MGMT<\/jats:italic> promoter methylation in cohort S (<jats:italic>p<\/jats:italic>\u2009=\u20090.0005), but did not reach significance in cohort C (<jats:italic>p<\/jats:italic>\u2009=\u20090.16). Significantly longer PFS was observed among patients with <jats:italic>MGMT<\/jats:italic> promoter\u2010methylated tumors (<jats:italic>p<\/jats:italic>\u2009=\u20090.002). Multivariate Cox regression analysis identified presence of <jats:italic>MGMT<\/jats:italic> promoter methylation as an independent variable associated with longer PFS. Together, this implies that <jats:italic>MGMT<\/jats:italic> promoter methylation is associated with response to single\u2010agent DTIC\/TMZ and longer PFS in disseminated cutaneous melanoma.<\/jats:p>","DOI":"10.1002\/ijc.29332","type":"journal-article","created":{"date-parts":[[2014,11,15]],"date-time":"2014-11-15T06:09:33Z","timestamp":1416031773000},"page":"2844-2853","source":"Crossref","is-referenced-by-count":51,"title":["MGMT promoter methylation is associated with temozolomide response and prolonged progression\u2010free survival in disseminated cutaneous melanoma"],"prefix":"10.1002","volume":"136","author":[{"given":"Rainer","family":"Tuominen","sequence":"first","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalyn","family":"Jewell","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cancer and Pathology, University of Leeds Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost J.","family":"van den Oord","sequence":"additional","affiliation":[{"name":"Department of General Medical Oncology University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Wolter","sequence":"additional","affiliation":[{"name":"Department of General Medical Oncology University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrika","family":"Stierner","sequence":"additional","affiliation":[{"name":"Department of Oncology Sahlgrenska University Hospital Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christer","family":"Lindholm","sequence":"additional","affiliation":[{"name":"Department of Oncology Ryhov County Hospital Jonkoping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Hertzman Johansson","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Lind\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemming","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Frostvik Stolt","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy","family":"Walker","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cancer and Pathology, University of Leeds Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Snowden","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cancer and Pathology, University of Leeds Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Newton\u2010Bishop","sequence":"additional","affiliation":[{"name":"Leeds Institute of Cancer and Pathology, University of Leeds Leeds United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Hansson","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Egyh\u00e1zi Brage","sequence":"additional","affiliation":[{"name":"Department of Oncology and Pathology Karolinska Institutet, Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1210093"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2013.06.027"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2011.06.002"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2000.18.1.158"},{"key":"e_1_2_6_7_1","first-page":"21","article-title":"Dacarbazine\u2010based chemotherapy for metastatic melanoma: thirty\u2010year experience overview","volume":"19","author":"Serrone L","year":"2000","journal-title":"J Exp Clin Cancer Res"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864-001-0033-5"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2009-0237"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0392"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.4969"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043331"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70025-7"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200011093431901"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26083"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605796"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.08.005"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biophys.36.040306.132646"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-144"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001662"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.49.6968"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.04.023"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0b013e328353a0ff"},{"key":"e_1_2_6_24_1","doi-asserted-by":"crossref","first-page":"654","DOI":"10.3892\/or.2012.1826","article-title":"Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first\u2010line temozolomide plus bevacizumab in the trial SAKK 50\/07","volume":"28","author":"Schraml P","year":"2012","journal-title":"Oncol Rep"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12220"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdt547"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e3283350578"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdi190"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.cmr.0000205019.23612.a1"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0803-5"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2013.05.011"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.10.8217"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3712"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1314469111"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-7-research0034"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fijc.29332","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.29332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T14:21:57Z","timestamp":1695997317000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.29332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,24]]},"references-count":36,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,6,15]]}},"alternative-id":["10.1002\/ijc.29332"],"URL":"https:\/\/doi.org\/10.1002\/ijc.29332","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,24]]}}}