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Genome-wide DNA methylation profiling of non-small cell lung carcinomasKeywords: DNA Methylation, Epigenetics, MethylCap, Next generation sequencing, Non-small cell lung Cancer Abstract: Analysis of the MethylCap-seq data revealed a strong positive correlation between replicate experiments and between paired tumor/lung samples. We identified 57 differentially methylated regions (DMRs) present in all NSCLC tumors analyzed by MethylCap-seq. While hypomethylated DMRs did not correlate to any particular functional category of genes, the hypermethylated DMRs were strongly associated with genes encoding transcriptional regulators. Furthermore, subtelomeric regions and satellite repeats were hypomethylated in the NSCLC samples. We also identified DMRs that were specific to two of the major subtypes of NSCLC, adenocarcinomas and squamous cell carcinomas.Collectively, we provide a resource containing genome-wide DNA methylation maps of NSCLC and their paired lung tissues, and comprehensive lists of known and novel DMRs and associated genes in NSCLC.Non-small cell lung carcinoma (NSCLC) is a common malignancy characterized by a worldwide high incidence and low survival rate [1]. NSCLC is a heterogenic disease which is broadly classified into three major histopathological subtypes: adenocarcinoma (ADC), squamous cell carcinoma (SCC) and large cell carcinoma (LCC). This heterogeneity poses challenges for diagnosis and treatment, since each subtype presents with a distinctive prognosis [2] and the choice of therapeutic regimen is predominantly based on tumor subtype and staging parameters [3]. The development of personalized diagnostics and therapy is leading the way to a new era that may see us overcome some of the difficulties in treating complex diseases such as NSCLC.In the past decade, comparative gene expression profiles of tumors have been extensively studied [4-6], yielding useful insights into the molecular hallmarks of carcinogenesis [7,8]. With the advent of next generation sequencing, genome-wide screening has become an attractive tool for profiling tumors versus lung tissues [7,9]. DNA methylation is a very stable epigenetic mark and next generation
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