Last week, Nature Communications published a paper from scientists at the University College London and other organizations studying methylation linked to variants in isocitrate dehydrogenase (IDH) genes in patients with bone cancer.
Lead author Paul Guilhamon and collaborators studied variants in IDH1 and IDH2, genes that are often mutated in a bone cancer called chondrosarcoma, as well as other cancers. The IDH variants are known to be associated with a hypermethylated phenotype in other cancers, so this effort focused on chondrosarcoma, which was found to also have more methylation than usual with the IDH variants. The variants function as an inhibitor of TET-mediated DNA demethylation, the authors report. Follow-on studies with chromatin immunoprecipitation and western blotting found a transcription factor that appears to be interacting with TET2 in the methylation regulation process.
In addition to an interesting advance in bone cancer biology, this paper offers a glimpse of a new use for our ThunderStorm™ Targeted Sequencing System. Guilhamon et al. used ThunderStorm with next-gen bisulfite sequencing to look at more than 1,000 CpG sites in wild type and mutant samples and assess methylation status. The ThunderStorm system was used for parallel amplification of the regions of interest, conducted with our picodroplet PCR technology. Through this work, they found a noticeable hypermethylation profile in the group with variants.
You can read the full paper here.