PMID- 20427748
OWN - NLM
STAT- MEDLINE
DCOM- 20100625
LR  - 20220812
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 74
IP  - 23
DP  - 2010 Jun 8
TI  - All the 1p19q codeleted gliomas are mutated on IDH1 or IDH2.
PG  - 1886-90
LID - 10.1212/WNL.0b013e3181e1cf3a [doi]
AB  - 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.
FAU - Labussiere, M
AU  - Labussiere M
AD  - UMR 975 INSERM-UPMC, Paris, France.
FAU - Idbaih, A
AU  - Idbaih A
FAU - Wang, X-W
AU  - Wang XW
FAU - Marie, Y
AU  - Marie Y
FAU - Boisselier, B
AU  - Boisselier B
FAU - Falet, C
AU  - Falet C
FAU - Paris, S
AU  - Paris S
FAU - Laffaire, J
AU  - Laffaire J
FAU - Carpentier, C
AU  - Carpentier C
FAU - Criniere, E
AU  - Criniere E
FAU - Ducray, F
AU  - Ducray F
FAU - El Hallani, S
AU  - El Hallani S
FAU - Mokhtari, K
AU  - Mokhtari K
FAU - Hoang-Xuan, K
AU  - Hoang-Xuan K
FAU - Delattre, J-Y
AU  - Delattre JY
FAU - Sanson, M
AU  - Sanson M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100428
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - EC 1.1.1.41 (IDH2 protein, human)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42. (IDH1 protein, human)
SB  - IM
CIN - Neurology. 2010 Jun 8;74(23):1848-9. PMID: 20445147
MH  - Brain Neoplasms/*genetics/mortality
MH  - Chromosomes, Human, Pair 1/*genetics
MH  - Follow-Up Studies
MH  - Genome-Wide Association Study/methods
MH  - Glioma/*genetics/mortality
MH  - Humans
MH  - Isocitrate Dehydrogenase/*genetics
MH  - Mutation/*genetics
MH  - Survival Analysis
EDAT- 2010/04/30 06:00
MHDA- 2010/06/26 06:00
CRDT- 2010/04/30 06:00
PHST- 2010/04/30 06:00 [entrez]
PHST- 2010/04/30 06:00 [pubmed]
PHST- 2010/06/26 06:00 [medline]
AID - WNL.0b013e3181e1cf3a [pii]
AID - 10.1212/WNL.0b013e3181e1cf3a [doi]
PST - ppublish
SO  - Neurology. 2010 Jun 8;74(23):1886-90. doi: 10.1212/WNL.0b013e3181e1cf3a. Epub 
      2010 Apr 28.