Overall, our data have identified a novel mechanism in which R132H mutation of the IDH1 gene serves as a tumor suppressor by promoting the recruitment of NK cells through CX3CL1/CX3CR1 chemotaxis.
Median PFS for patients with IDH-mutant 1p19q-codeleted, IDH-mutant 1p19q-intact, and IDH1-R132H-wildtype tumors were 113 months, 56 months, and not reached, respectively.
All tumor specimens were evaluated for miRNA-26a expression, MGMT promoter methylation, and IDH1 R132H mutation status, and the results were correlated with the clinical data.
Selecting cases with negative BCAT1 and R132H-mutant IDH1 staining for DNA sequencing of IDH1/2 genes could improve the cost-effectiveness of detecting IDH mutations particularly in tumors with low IDH mutation rates, and confine the need of 1p/19q assay in IDH-mutant tumors.
Tumors were generated by inactivating <i>Pten</i> and <i>p53</i> in forebrain progenitors and compared with tumors additionally expressing the Idh1 R132H mutation.
Paraffin-embedded tumor tissues were subjected to FISH analysis, and the corresponding frozen tissues from the same tumors were evaluated for aCGH and/or WES for 1p/19q co-deletion and other genetic parameters, which included IDH1-R132H, ATRX, TP53, CIC, and NOTCH1 mutations and MGMT methylation status.
Low-grade gliomas (WHO II/III) had lower xCT expression than glioblastoma (p = 0.001), and tumors without IDH1 R132H mutation tended to have higher xCT levels (p = 0.07).
The tumor samples were histologically reviewed and subsequently assessed for p53 and survivin expression and the presence of the IDH R132H mutation by immunohistochemistry. p53 expression levels and survivin subcellular localization patterns were correlated with histological classification and clinical outcome.
Our retrospective analysis suggested that the presence of an IDH1 (R132H) mutation, frontal tumor location, and WHO grade of the initial tumor are associated with OS after progression to sGBM.
Genetic analysis of both the supratentorial and spinal tumours revealed R132H IDH1 mutations, providing evidence that the spinal cord lesion had spread from the supratentorial tumour.
Significantly higher mean SWI-LIV values were found in HGG compared to LGG (92.7 versus 30.8; p < 0.0001), IDH1-R132H negative compared to IDH1-R132H positive gliomas (109.9 versus 38.3; p < 0.0001) and tumours with significant CE compared to non-significant CE (120.1 versus 39.0; p < 0.0001).
Patients benefit more from chemoradiation than radiation alone, especially those with tumour IDH1 Arg132His mutations; gross total resection of the tumour, including tumours with IDH mutations, is associated with prolonged survival.
Due to the IDH1 R132H mutation, the patient was diagnosed with diffuse astrocytoma WHO grade II and underwent successful gross total resection of this near-eloquently located tumor.
In the large majority (>80%) of tumors IDH mutations, both IDH1-R132H and the non-canonical ones, were present in the large majority (>80%) of neoplastic cells.
Discordant cases included those with insufficient amounts of circulaating tumor DNA in plasma and cases in which known driver mutations (e.g., isocitrate dehydrogenase (NADP(+)), 1 systolic gene [IDH1] R132H, kinesin family member 5B gene [KIF5b-ret proto-oncogene [RET], or MNNG HOS Transforming gene [MET] exon 14) were found in the plasma but were not interrogated by routine tissue analyses.