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Our single nucleotide polymorphism (SNP) array identified 8p copy number losses localized to an 8.4 Mb minimal deleted region (MDR) in 36% of CC. The 8p MDR was associated with tumor size, treatment outcome, and with multiple HPV infections. Genetic, epigenetic, and expression analyses of candidate genes at MDR identified promoter hypermethylation and\/or inactivation of decoy receptors <jats:italic>TNFRSF10C<\/jats:italic> and <jats:italic>TNFRSF10D<\/jats:italic> in the majority of CC patients. <jats:italic>TNFRSF10C<\/jats:italic> methylation was also detected in precancerous lesions suggesting that this change is an early event in cervical tumorigenesis. We further demonstrate here that CC cell lines exhibiting downregulated expression of TNFRSF10C and\/or TNFRSF10D effectively respond to TRAIL\u2010induced apoptosis and this affect was synergistic in combination with DNA damaging chemotherapeutic drugs. We show that the CC cell lines harboring epigenetic inactivation of TRAIL decoy receptors effectively activate downstream caspases suggesting a critical role of inactivation of these genes in efficient execution of extrinsic apoptotic pathway and therapy response. Therefore, these findings shed new light on the role of genetic\/epigenetic defects in TRAIL decoy receptor genes in the pathogenesis of CC and provide an opportunity to explore strategies to test decoy receptor gene inactivation as a biomarker of response to Apo2L\/TRAIL\u2010combination therapy. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/gcc.22325","type":"journal-article","created":{"date-parts":[[2015,11,6]],"date-time":"2015-11-06T10:50:10Z","timestamp":1446807010000},"page":"177-189","source":"Crossref","is-referenced-by-count":20,"title":["Epigenetic inactivation of <scp>TRAIL<\/scp> decoy receptors at 8p12\u201021.3 commonly deleted region confers sensitivity to <scp>A<\/scp>po2L\/<scp>trail<\/scp>\u2010<scp>C<\/scp>isplatin combination therapy in cervical cancer"],"prefix":"10.1002","volume":"55","author":[{"given":"Gopeshwar","family":"Narayan","sequence":"first","affiliation":[{"name":"Department of Pathology and Cell Biology Columbia University Medical 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