An analysis of the prognostic value of IDH1 (isocitrate dehydrogenase 1) mutation in Polish glioma patients.
OBJECTIVE
IDH1 (isocitrate dehydrogenase 1) is a potential biomarker and drug target. Genomic and epigenetic data on astrocytoma have demonstrated that the IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Furthermore, recent studies have also indicated that a mutant IDH1 inhibitor induced demethylation of histone H3K9me3 and expression of genes associated with gliogenic differentiation. As the presence of the p.R132H mutation in the IDH1 gene seems to be a more powerful prognostic marker than O(6)-methylguanine-DNA methyltransferase promoter status, we evaluated the presence of IDH1 mutation in Polish patients with astrocytoma, glioblastoma, oligoastrocytoma, ganglioglioma, oligodendroglioma, and ependymoma.


METHODS
The IDH1 mutation status at codon 132 was determined using a mouse monoclonal antibody specific for the R132H mutation, direct sequencing, and Co-amplification at Lower Denaturation Temperature (COLD) polymerase chain reaction (PCR) high-resolution melting-curve analysis (HRM).


RESULTS
Wild-type (WT) IDH1 was detected in cases with a World Health Organization (WHO) grade I astrocytoma. The IDH1 c.G395A; p.R132H mutation was observed in 56 and 94 % of grade II and grade III astrocytoma cases, respectively. Significant differences in the median overall survival were observed in astrocytoma patients grouped on the basis of the presence of IDH1 mutation: survival was 24 months longer in grade II astrocytoma and 12 months longer in glioblastoma. Overall survival was compared between grade II astrocytoma patients with low or high expression of the mutant protein. Interestingly, lower R132H expression correlated with better overall survival.


CONCLUSIONS
Our results indicate the usefulness of assessing the R132H IDH1 mutation in glioma patients: the presence or absence of the R132H mutation can help pathologists to distinguish pilocytic astrocytomas (IDH1 WT) from diffuse ones (R132H IDH1/WT). Moreover, low IDH1 p.R132H expression was related to better prognosis. This clinical implication appears to be important for personalization of prognosis and treatment by oncologists.
Molecular Oncology and Genetics Unit, Department of Tumor Pathology and Pathomorphology, The Franciszek Lukaszczyk Oncology Center, dr I. Romanowskiej 2, 85-796, Bydgoszcz, Poland, lewandowskam@co.bydgoszcz.pl.
Marzena Anna
MA
Lewandowska
Jacek
J
Furtak
Tadeusz
T
Szylberg
Krzysztof
K
Roszkowski
Wiesława
W
Windorbska
Joanna
J
Rytlewska
Wojciech
W
Jóźwicki
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D005910:Glioma / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D009367:Neoplasm Staging; D017354:Point Mutation; D011044:Poland; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D055815:Young Adult
D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human