Academic Journals Database
Disseminating quality controlled scientific knowledge

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

ADD TO MY LIST
 
Author(s): Carvalho Rejane | Haberle Vanja | Hou Jun | van Gent Teus | Thongjuea Supat | van IJcken Wilfred | Kockx Christel | Brouwer Rutger | Rijkers Erikjan | Sieuwerts Anieta | Foekens John | van Vroonhoven Mirjam | Aerts Joachim | Grosveld Frank | Lenhard Boris | Philipsen Sjaak

Journal: Epigenetics & Chromatin
ISSN 1756-8935

Volume: 5;
Issue: 1;
Start page: 9;
Date: 2012;
Original page

Keywords: DNA Methylation | Epigenetics | MethylCap | Next generation sequencing | Non-small cell lung Cancer

ABSTRACT
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 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. 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.

Tango Jona
Tangokurs Rapperswil-Jona

     Affiliate Program