All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2.
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.
Labussière
M
M
UMR 975 INSERM-UPMC, Paris, France.
Idbaih
A
A
Wang
X-W
XW
Marie
Y
Y
Boisselier
B
B
Falet
C
C
Paris
S
S
Laffaire
J
J
Carpentier
C
C
Crinière
E
E
Ducray
F
F
El Hallani
S
S
Mokhtari
K
K
Hoang-Xuan
K
K
Delattre
J-Y
JY
Sanson
M
M
D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study / Q000379:methods; D005910:Glioma / Q000235:genetics* / Q000401:mortality; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016019:Survival Analysis
C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human