The single nucleotide polymorphism (SNP) rs11554137 (IDH1<sup>105GGT</sup>) at codon 105 of IDH1 has been reported in patients with several tumor types, including those with glioma.
For this study, 164 cases of glioma were evaluated immunohistochemically for IDH1 mutations (R132H and R132S) using anti-IDH1 mAbs (HMab-1 and SMab-1).
Mutations in the isocitrate dehydrogenase (IDH) 1 gene are commonly found in human glioma, with the majority of low-grade gliomas harboring a recurrent point mutation (IDH1 R132H).
Additionally, 5-aza enhances the therapeutic effect of the DNA damaging agent TMZ in both subcutaneous and orthotopic PDX models of IDH1 R132H mutant glioma.
In 1 case, an IDH1 R132H-mutant glioma was misdiagnosed as a demyelinating condition by frozen section histology during the intraoperative consultation, and no resection was performed pending the final pathology report.
<i>IDH1</i> mutations only affected brainstem gliomas (6/24 vs 0/78; <i>p</i> = 7.5 × 10<sup>-5</sup>), were mostly non-R132H (contrasting with hemispheric gliomas, <i>p</i> = 0.0001), and were associated with longer survival (54 vs 12 months).
These results support a role for Fn14 in the more aggressive and invasive phenotype associated with IDH1 WT tumors and indicate that the low levels of Fn14 gene expression noted in IDH1 R132H mutant gliomas may be due to epigenetic regulation via changes in DNA methylation.
Patients/Methods In a prospective cohort study, intratumoral IDH1 R132H mutation and podoplanin were determined in brain tumor specimens (mainly glioma) by immunohistochemistry.
Sequencing for rare IDH mutations is advised for A,NOS and OA,NOS groups, but not for the IDH1(R132H)-non-mutant diffuse gliomas with 1p/19q co-deletion.
Recurrent heterozygous mutation of isocitrate dehydrogenase 1 gene (<i>IDH1</i>), predominantly resulting in histidine substitution at arginine 132, was first identified in glioma.
In cases tested by DNA sequencing, the fraction of non-R132H mutations was 5.4%, which included only 2 high-grade gliomas in patients ≥55 years (0.9%).
Our results suggest that the pathogenesis of multicentric gliomas is different from the mutant IDH1-R132H pathogenesis of lower-grade glioma and secondary glioblastomas.
This study is to understand the effects of IDH1 R132H mutation in gliomagenesis and to develop new strategies to treat glioma with IDH1 R132H mutation.