Analysis of Genomewide and Locus-specific DNA Methylation Patterns in Disease and Development

Epigenetic modifications such as post-transcriptional histone modifications, non-coding RNAs, and DNA methylation lay the regulatory landscape for the gene expression programs in a cell. Knowledge about these various aspects of the epigenome is crucial for understanding the phenotypic variation between healthy and diseased cells, which is currently one of the main challenges in biomedical research. DNA methylation is a stable and heritable covalent modification, and in humans, mostly affects cytosines in the context of CpG dinucleotides. DNA methylation can be detected and quantified using a number of technologies, including genomewide screening methods such as second-generation sequencing and high-throughput epigenotyping, in addition to locus- or gene-specific high resolution analysis using Pyrosequencing or quantitative methylation-specific PCR-based approaches. Some of these technologies can be applied to analyzing DNA methylation patterns in frozen tissues and FFPE samples, as well as in body fluids such as urine, plasma, and serum obtained through non-invasive procedures.

DNA methylation might be of great potential for many applications, since DNA methylation-based biomarkers have proven to be more specific and sensitive than commonly used protein biomarkers. In this presentation, I will discuss technologies for analyzing DNA methylation and the practical considerations and advantages for developing DNA methylation-based markers for various clinical and biological questions. I will also address research into the use of these markers for detecting disease or predicting outcome or treatment response in the context of cancer-focused laboratory examples, in addition to their potential use in other complex diseases and model systems.

Dr. Jörg Tost

Jörg Tost received his Ph.D. in genetics from the University of Saarbrücken (Germany) in 2004, devising novel methods for analyzing haplotypes and DNA methylation patterns. He was a postdoctoral researcher in the technology development department of the Centre National de Génotypage (CNG, Evry, France), and since 2006 heads the Epigenetics Laboratory, which is part of the CEA-Institut de Génomique at the CNG. The team develops and applies technologies for analyzing DNA methylation and other epigenetic modifications at high resolution both genomewide and at target loci, in addition to developing bioinformatic tools for processing such data. The laboratory pioneered the use of Pyrosequencing technology for analyzing DNA methylation and devised a number of novel methods using this technology. The main focus of the Epigenetics Laboratory has been analyzing DNA methylation patterns implicated in tumorigenesis and other complex diseases and development, and understanding the interplay between genetic and epigenetic variation.

Dr. Tost is author or co-author of 54 publications, 46 of which have appeared in Medline-listed journals. He is editor of the book Epigenetics (Horizon Scientific Press, 2008), as well as the 2nd edition of DNA Methylation: Methods and Protocols, from the Methods in Molecular Biology series (2009). He is also senior editor of the journal Epigenomics.