IDH1/2 mutations in WHO grade II astrocytomas associated with localization and seizure as the initial symptom.
BACKGROUND
Seizures are the most common initial symptom in patients with low-grade glioma and their occurrence strongly depends on the tumor location. The majority of low-grade gliomas reveal mutations in the genes encoding isocitrate-dehydrogenase 1 (IDH1) or 2 (IDH2). These mutations are associated with metabolic changes that are potentially epileptogenic. We investigated the correlation between IDH1/2 mutations and tumor localization and seizure as the initial symptom.


METHODS
This retrospective study included patients with a diagnosis of WHO grade II astrocytoma and cortical infiltration and in whom initial symptoms were documented and biopsy tissue was available for IDH1/2 analysis. IDH1/2 mutation analysis was performed by direct sequencing or by immunohistochemistry with an antibody which detects mutated protein IDH1 R132H. Sequencing was carried out if immunohistochemistry was negative. IDH1/2 status was defined as mutated if either of these investigations were positive.


RESULTS
Seventy-nine patients were included. IDH1 or IDH2 mutation was present in 63 (80%) patients who on average were younger than patients without IDH1/2 mutation (40 vs. 47 years, p=0.0331, t-test). IDH1/2 mutations were associated with frontal tumor location (p=0.0202). All 12 tumors in the insula revealed IDH1/2 mutations. Seizure as the initial symptom was recorded in 57 (72%) patients and was associated with IDH1 or IDH2 mutation by multivariate analysis (OR 22.563, p=0.0019).


CONCLUSIONS
In WHO grade II astrocytomas, IDH1/2 mutations mostly occur in tumors infiltrating the frontal lobe. Seizure as the initial symptom is associated with IDH1 or IDH2 mutation.
Department of Neurosurgery, University Medical Center Göttingen, 37075 Göttingen, Germany. florian.stockhammer@med.uni-goettingen.de
Florian
F
Stockhammer
Martin
M
Misch
Hans-Joachim
HJ
Helms
Ulrike
U
Lengler
Friedrich
F
Prall
Andreas
A
von Deimling
Christian
C
Hartmann
D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D012189:Retrospective Studies; D012640:Seizures / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human