Contributions of IDH Mutation to Gliomagenesis

R132H mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) are considered to be the earliest and most prevalent alterations in lower grade glioma. We are interested in how these mutations contribute to the development of lower-grade gliomas.

IDH1 mutations are the defining genetic alteration in lower-grade gliomas.  IDH1 mutation in turn leads to production of the oncometabolite 2-hydroxyglutarate (2HG).  Although 2HG is recognized to compete with alpha-ketoglutarate and to inhibit the activity of enzymes that regulate the epigenetic state of the cell, the exact alterations that contribute to gliomagenesis remain largely undefined.  We use genetically defined cell-based systems to uncover these potentially therapeutically targetable pathways.

Related Publications

Mukherjee J, Johannessen TA, Ohba S, Chow TT, Jones LE, Pandita A, Pieper RO. Mutant IDH1 cooperates with ATRX loss to drive the alternative lengthening of telomere (ALT) phenotype in glioma. Cancer Res. 2018 Jun 1;78(11):2966-2977. Epub 2018 Mar 15.

Ohba S, Mukherjee J, Johannessen TC, Mancini A, Mazor T, Wood M, Pieper, RO. Mutant IDH1 expression drives TERT promoter reactivation as part of the cellular transformation process. Cancer Res. 2016 Nov 15;76(22):6680-6689. Epub 2016 Oct 6.