IDH1 Mutations in Gliomas: When an Enzyme Loses Its Grip

Tankyrase Loses Its Grip on SH3BP2 in Cherubism

Cherubism, a case of bone remodeling gone haywire, is associated with mutations in the adaptor protein SH3BP2. Two papers in this issue of Cell (Guettler et al. and Levaot et al.) demonstrate that these mutations disrupt the interaction between SH3BP2 and Tankyrase and describe rules for substrate recognition by this poly(ADP-ribose) polymerase. Establishing such rules paves the way to identify...

Metabolism, gliomas, and IDH1.

Enzyme Redesign Guided by Cancer-Derived IDH1 Mutations

Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases to homologous residues in the active sites of homoisocitrate dehydrogenases to derive enzymes that catalyze the conversion of 2-oxoadipate to (R)-2-hydroxyadipate, a critical step for adipic acid production. Thus, we provide a prototypic example ...

Comparative study of IDH1 mutations in gliomas by immunohistochemistry and DNA sequencing.

BACKGROUND Mutations involving isocitrate dehydrogenase 1 (IDH 1) occur in a high proportion of diffuse gliomas, with implications on diagnosis and prognosis. About 90% involve exon 4 at codon 132, replacing amino acid arginine with histidine (R132H). Rarer ones include R132C, R132S, R132G, R132L, R132V, and R132P. Most authors have used DNA-based methods to assess IDH1 status. Preliminary stud...

Comparison of immunohistochemistry and DNA sequencing for the detection of IDH1 mutations in gliomas.

We read with interest a recent paper published by Chen et al on building a multivariable model to predict the likelihood of an IDH1/2 mutation in diffuse gliomas. Incorporating patient age, glioblastoma diagnosis, and prior history of grade II or III gliomas, the model was shown to have high sensitivity and specificity for predicting the presence of an IDH1/2 mutation, either with or without an...