title: Identification of an epigenetic profile classifier that is associated with survival in head and neck cancer.
abstract: Panels of prognostic biomarkers selected using candidate approaches often do not validate in independent populations, so additional strategies are needed to identify reliable classifiers. In this study, we used an array-based approach to measure DNA methylation and applied a novel method for grouping CpG dinucleotides according to well-characterized genomic sequence features. A hypermethylation profile among 13 CpG loci, characterized by polycomb group target genes, mammalian interspersed repeats, and transcription factor-binding sites (PcG/MIR/TFBS), was associated with reduced survival (HR, 3.98; P = 0.001) in patients with head and neck squamous cell carcinoma. This association was driven by CpGs associated with the TAP1 and ALDH3A1 genes, findings that were validated in an independent patient group (HR, 2.86; P = 0.04). Together, the data not only elucidate new potential targets for therapeutic intervention in head and neck cancer but also may aid in the identification of poor prognosis patients who may require more aggressive treatment regimens.
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Poage
authors.forename: Rondi A
authors.initials: RA
authors.lastname: Butler
authors.forename: E Andrés
authors.initials: EA
authors.lastname: Houseman
authors.forename: Michael D
authors.initials: MD
authors.lastname: McClean
authors.forename: Heather H
authors.initials: HH
authors.lastname: Nelson
authors.forename: Brock C
authors.initials: BC
authors.lastname: Christensen
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019295:Computational Biology; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D011379:Prognosis; D016016:Proportional Hazards Models; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; C073119:TAP1 protein, human; C480021:ALDH3A1 protein, human; D000444:Aldehyde Dehydrogenase