PubMed · 7458369
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
J M Bonnetblanc, J L Delrous, G Catanzano, A Licout, J Roux. 1981. Multiple clear cell acanthoma.. https://doi.org/10.1001/archderm.1981.01650010005002
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
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 < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC.
BACKGROUND: Currently, the classification of oral squamous cell carcinoma (OSCC) depends heavily on the clinical and pathologic examination of tissue. This system can lead to the classification of potentially heterogeneous tumors into single groups when they may have different degrees of aggressiveness. No system to date has incorporated genetic changes as a factor by which to classify OSCC tumors. METHODS: To test the hypothesis that OSCC has a genome-wide genetic expression profile that differs from normal oral tissue and that transcriptional expression profiling can be used to characterize the heterogeneity among tumors, the authors examined the genetic expression profiles of 26 invasive squamous cell carcinomas of the oral cavity and oropharynx, 2 premalignant lesions, and 18 normal oral tissue samples using oligonucleotide arrays that contained probes representing approximately 7000 full-length human genes. RESULTS: Using hierarchical clustering analysis, the data show that oral carcinomas are distinguishable from normal oral tissue based on genome-wide transcriptional expression patterns. However, there is genetic expression profile heterogeneity among tumors of a particular histopathologic grade and stage. In addition, using a statistical approach that integrated normalization and regression analysis, the authors found 314 genes that were expressed differentially in the OSCC samples with statistical significance (P <or= 0.05). Of these, 239 genes were overexpressed in the OSCC samples, whereas 75 genes were down-regulated. CONCLUSIONS: No statistically significant differences in gene expression were found between early-stage disease and late-stage disease or between metastatic tumors and nonmetastatic tumors. The implications of these findings for the prediction of clinical outcome and for the discovery of new OSCC tumor markers are discussed.
The locus for a syndrome of focal palmoplantar keratoderma (Tylosis) associated with squamous cell oesophageal cancer (TOC) has been mapped to chromosome 17q25, a region frequently deleted in sporadic squamous cell oesophageal tumours. Further haplotype analysis described here, based on revised maps of marker order, has reduced the TOC minimal region to a genetic interval of 2 cM limited by the microsatellite markers D17S785 and D17S751. Partial sequence data and complete physical maps estimate the actual size of this region to be only 0.5 Mb. This analysis allowed the exclusion of proposed candidate tumour suppressor genes including MLL septin-like fusion (MSF), survivin, and deleted in multiple human cancer (DMC1). Computer analysis of sequence data from the minimal region identified 13 candidate genes and the presence of 50-70 other 'gene fragments' as ESTs and/or predicted exons and genes. Ten of the characterized genes were assayed for mutations but no disease-specific alterations were identified in the coding and promoter sequences. This region of chromosome 17q25 is, therefore, relatively gene-rich, containing 13 known and possibly as many as 50 predicted genes. Further mutation analysis of these predicted genes, and others possibly residing in the region, is required in order to identify the elusive TOC locus.