Functional and topographic effects on DNA methylation in IDH1/2 mutant cancers Journal Article

   


Authors: Bledea, R.; Vasudevaraja, V.; Patel, S.; Stafford, J.; Serrano, J.; Esposito, G.; Tredwin, L. M.; Goodman, N.; Kloetgen, A.; Golfinos, J. G.; Zagzag, D.; Weigelt, B.; Iafrate, A. J.; Sulman, E. P.; Chi, A. S.; Dogan, S.; Reis-Filho, J. S.; Chiang, S.; Placantonakis, D.; Tsirigos, A.; Snuderl, M.
Article Title: Functional and topographic effects on DNA methylation in IDH1/2 mutant cancers
Abstract: IDH1/2 mutations are early drivers present in diverse human cancer types arising in various tissue sites. IDH1/2 mutation is known to induce a global hypermethylator phenotype. However, the effects on DNA methylation across IDH mutant cancers and functionally different genome regions, remain unknown. We analyzed DNA methylation data from IDH1/2 mutant acute myeloid leukemia, oligodendroglioma, astrocytoma, solid papillary breast carcinoma with reverse polarity, sinonasal undifferentiated carcinoma and cholangiocarcinoma, which clustered by their embryonal origin. Hypermethylated common probes affect predominantly gene bodies while promoters in IDH1/2 mutant cancers remain unmethylated. Enhancers showed global hypermethylation, however commonly hypomethylated enhancers were associated with tissue differentiation and cell fate determination. We demonstrate that some chromosomes, chromosomal arms and chromosomal regions are more affected by IDH1/2 mutations while others remain resistant to IDH1/2 mutation induced methylation changes. Therefore IDH1/2 mutations have different methylation effect on different parts of the genome, which may be regulated by different mechanisms. © 2019, The Author(s).
Journal Title: Scientific Reports
Volume: 9
ISSN: 2045-2322
Publisher: Nature Publishing Group  
Date Published: 2019-11-14
Start Page: 16830
Language: English
DOI: 10.1038/s41598-019-53262-7
PUBMED: 31727977
PROVIDER: scopus
PMCID: PMC6856069
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85075044035&doi=10.1038%2fs41598-019-53262-7&partnerID=40&md5=38f72b52145463f11b3e11a380c68de9
Notes: Article -- Source: Scopus
Altmetric
What is Altmetric?
Citation Impact
What is Dimensions Citation Badge?
BMJ Impact Analytics
MSK Authors
  1. Snjezana Dogan
    190 Dogan
  2. Britta Weigelt
    637 Weigelt
  3. Jorge Sergio Reis-Filho
    640 Reis-Filho
  4. Sarah Chiang
    146 Chiang
Related MSK Work