1. Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma.
- Author
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Ben-Dayan, Miriam M, Ow, Thomas J, Belbin, Thomas J, Wetzler, Joshua, Smith, Richard V, Childs, Geoffrey, Diergaarde, Brenda, Hayes, D Neil, Grandis, Jennifer R, Prystowsky, Michael B, and Schlecht, Nicolas F
- Subjects
Humans ,Carcinoma ,Squamous Cell ,Oropharyngeal Neoplasms ,Neoplasm Recurrence ,Local ,Prognosis ,Prospective Studies ,Sequence Analysis ,RNA ,DNA Methylation ,Epigenesis ,Genetic ,Gene Expression Regulation ,Neoplastic ,Up-Regulation ,Female ,Male ,Cyclin-Dependent Kinase Inhibitor p16 ,Cyclin-Dependent Kinase Inhibitor p18 ,Transcriptional Activation ,CDKN2A ,gene transcription ,larynx cancer ,methylation ,p14(ARF) ,p16(INK4a) ,tumor biomarkers ,Carcinoma ,Squamous Cell ,Epigenesis ,Genetic ,Gene Expression Regulation ,Neoplastic ,Neoplasm Recurrence ,Local ,Sequence Analysis ,RNA ,Biochemistry and Cell Biology ,Oncology and Carcinogenesis - Abstract
We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P
- Published
- 2017