All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2

Abstract

Background: Recently, the gene encoding the human cytosolic NADPH-dependent isocitrate dehydrogenase (IDH1) was reported frequently mutated in gliomas. Rare mutations were also found in the sequence of the mitochondrial isoform IDH2.

Methods: In a series of 764 gliomas genome-wide characterized, we determined the presence of mutations in the sequences of both IDH1 and IDH2 genes by direct sequencing.

Results: We found that all tumors with complete 1p19q codeletion (n = 128) were mutated in the IDH1 (118) or IDH2 (10) gene. This 100% mutation rate contrasted strikingly with other gliomas exhibiting either variable 1p and 19q alterations (n = 159, IDH1/IDH2 mutation rate of 33%) or no 1p19q alteration (n = 477, IDH1/IDH2 mutation rate 32%). Our data also confirm the prognostic impact of IDH1/IDH2 mutation in gliomas whatever grade considered: patients harboring mutations of IDH1/IDH2 have an improved median overall survival. Moreover, in WHO grade II and III gliomas, 3 groups with significantly different outcomes were identified according to their 1p19q and IDH1/IDH2 statuses. Tumors carrying both alterations had longer overall survival than their nonmutated counterpart.

Conclusions: This exclusive association suggests a new mechanism of tumorigenesis. Perhaps the IDH1/IDH2 mutation is a prerequisite for the occurrence of the t(1;19) translocation, or it is required for the 1p19q codeleted cells to acquire a tumor phenotype.