Genome-wide DNA methylation profiling of non-small cell lung carcinomas

Rejane Hughes Carvalho, V Haberle, Jun Hou, T Gent, S Thongjuea, Wilfred van Ijcken, Christel Kockx, Rutger Brouwer, HWJ Rijkers, Anieta Sieuwerts, John Foekens, Mirjam Van den Hout - van Vroonhoven, Joachim Aerts, Frank Grosveld, B Lenhard, Sjaak Philipsen

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Abstract

Background: Non-small cell lung carcinoma (NSCLC) is a complex malignancy that owing to its heterogeneity and poor prognosis poses many challenges to diagnosis, prognosis and patient treatment. DNA methylation is an important mechanism of epigenetic regulation involved in normal development and cancer. It is a very stable and specific modification and therefore in principle a very suitable marker for epigenetic phenotyping of tumors. Here we present a genome-wide DNA methylation analysis of NSCLC samples and paired lung tissues, where we combine MethylCap and next generation sequencing (MethylCap-seq) to provide comprehensive DNA methylation maps of the tumor and paired lung samples. The MethylCap-seq data were validated by bisulfite sequencing and methyl-specific polymerase chain reaction of selected regions. Results: 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 satelli Conclusions: 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.
Original languageUndefined/Unknown
JournalEpigenetics & Chromatin
Volume5
DOIs
Publication statusPublished - 2012

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