IDH1 mutations in low-grade astrocytomas predict survival but not response to temozolomide.
BACKGROUND
Mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) have been implicated in tumorigenesis of gliomas. Patients with high-grade astrocytomas with IDH1 or IDH2 mutations were reported to have a better survival, but it is unknown if this improved survival also holds for low-grade astrocytoma and whether these mutations predict outcome to specific treatment.


METHODS
We retrospectively investigated the correlation of IDH1 and IDH2 mutations with overall survival and response to temozolomide in a cohort of patients with dedifferentiated low-grade astrocytomas treated with temozolomide at the time of progression after radiotherapy.


RESULTS
IDH1 mutations were present in 86% of the 49 progressive astrocytomas. No mutations in IDH2 were found. Presence of IDH1 mutations were early events and significantly improved overall survival (median survival 48 vs 98 months), but did not affect outcome of temozolomide treatment.


CONCLUSIONS
These results indicate that IDH1 mutations identify a subgroup of gliomas with an improved survival, but are unrelated to the temozolomide response.
Dubbink
H J
HJ
Department of Pathology, Josephine Nefkens Institute, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Taal
W
W
van Marion
R
R
Kros
J M
JM
van Heuvel
I
I
Bromberg
J E
JE
Zonnenberg
B A
BA
Zonnenberg
C B L
CB
Postma
T J
TJ
Gijtenbeek
J M M
JM
Boogerd
W
W
Groenendijk
F H
FH
Smitt
P A E Sillevis
PA
Dinjens
W N M
WN
van den Bent
M J
MJ
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D000077204:Temozolomide