A total of 135 cases consisted of 38 IDH-mutant [17 astrocytoma (AC), 13 oligodendroglioma (OD) and eight glioblastoma (GBM)], 87 IDH-wildtype (six AC, three OD and 78 GBM), and 10 diffuse midline glioma, H3K27M-mutant.
As of 2016, isocitrate dehydrogenase (IDH)-1 and IDH-2 mutations are part of the definition of an oligodendroglioma and may be seen in a significant subset of grade II-IV fibrillary astrocytomas.
Patients with IDH wild type anaplastic astrocytoma and glioblastoma had a significantly shorter median PFS (19.3 months vs. NR, p = 0.001) and median OS (43.5 months vs NR, p = 0.007) than those with IDH mutated grade III anaplastic astrocytoma and oligodendroglioma.
Indeed, 1p36/19q13 has been shown successively to predict increased chemosensitivity and better prognosis, to be associated with frontal location in brain and classic oligodendroglioma morphology, to be mutually exclusive with high-level gene amplification, to be actually whole chromosome arms 1p/19q codeletion, to mediate a t(1;19)(q10;p10) and to be associated with IDH mutations.
Three GBM-O samples had IDH1 (p.R132H) mutations; two of these also demonstrated 1p/19q co-deletion and had a proneural transcriptional profile, a molecular signature characteristic of oligodendroglioma.
We first compared tumor tissues (TT) and minimally infiltrated parenchymal tissues (MIT) of four IDH1-mutated oligodendrogliomas to verify whether proteins specific to oligodendroglioma tumor cells could be identified from one patient to another.
The mutation analysis performed on the latter case with DNA separately sampled from the oligodendroglioma- like area and the astrocytoma-like area detected IDH1G395A in both areas.
We analyzed markers, including IDH mutation(IDHmut), 1p19q codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression, and outcomes in 159 patients with WHO grade II oligodendroglioma, oligoastrocytoma, and astrocytoma (2003-2012).
Trisomy of chromosome 7 in IDH mutated astrocytoma and PTEN mutations in IDH mutated oligodendroglioma are potential markers of poor prognosis, but require confirmation in larger series.
Secondly, when analyzed in molecular subgroups, we were similarly unable to detect a significant PFS or OS benefit in IDH MT/codel subgroup (N = 269; HR 1.47; 95% CI 0.92-2.34; P = 0.11 and HR 1.54; 95% CI 0.78-3.05; P = 0.21, respectively), oligodendroglioma with IDH MT/codel subgroup (N = 233; HR 1.33; 95% CI 0.79-2.21; P = 0.28 and HR 1.16; 95% CI 0.53-2.54; P = 0.70, respectively) or other relevant subgroups.
Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP.
Our data reveal that the methylation profiles in 23 of the 25 GC tumors corresponded to either IDH mutant astrocytoma (n = 6), IDH mutant and 1p/19q codeleted oligodendroglioma (n = 5), or IDH wild-type glioblastoma including various molecular subgroups, i.e., H3F3A-G34 mutant (n = 1), receptor tyrosine kinase 1 (RTK1, n = 4), receptor tyrosine kinase 2 (classic) (RTK2, n = 2) or mesenchymal (n = 5) glioblastoma groups.
We analyzed markers, including IDH mutation(IDHmut), 1p19q codeletion(1p19qcodel), ATRX expression loss(ATRX loss) and p53 overexpression, and outcomes in 159 patients with WHO grade II oligodendroglioma, oligoastrocytoma, and astrocytoma (2003-2012).
Furthermore, identification of a common IDH1 mutation in enchondroma and oligodendroglioma-matched pair specimens supports the hypothesis that IDH1/2 mosaicism initiates tumorigenesis.
Secondly, when analyzed in molecular subgroups, we were similarly unable to detect a significant PFS or OS benefit in IDH MT/codel subgroup (N = 269; HR 1.47; 95% CI 0.92-2.34; P = 0.11 and HR 1.54; 95% CI 0.78-3.05; P = 0.21, respectively), oligodendroglioma with IDH MT/codel subgroup (N = 233; HR 1.33; 95% CI 0.79-2.21; P = 0.28 and HR 1.16; 95% CI 0.53-2.54; P = 0.70, respectively) or other relevant subgroups.
A better prognosis was significantly associated with combined IDH1 mutation and MGMT methylation status (both positive vs both negative, HR 0.079 [95% CI 0.008-0.579], p=0.012), as well as histology (OG vs DA and OA, HR 0.158 [95% CI 0.022-0.674], p=0.011) and tumor size (<6 cm vs ≥6 cm, HR 0.120 [95% CI 0.017-0.595], p=0.008).
We evaluated nuclear cMYC protein levels and IDH1 (R132H) by immunohistochemistry in patients with oligodendroglioma/oligoastrocytomas (n = 20), astrocytomas (grade II) (n = 19), anaplastic astrocytomas (n = 21) or glioblastomas (n = 111).
One hundred twenty-six tumors could be classified: 20 as type II (IDH mutation [mut], "astrocytoma"), 49 as type I (1p/19q codeletion, "oligodendroglioma"), 55 as type III (7+/10q- or TERTmut and 1p/19q intact, "glioblastoma"), and 2 as childhood glioblastoma (H3F3Amut), leaving 7 unclassified (total 91% classified).
Patients with IDH wild type anaplastic astrocytoma and glioblastoma had a significantly shorter median PFS (19.3 months vs. NR, p = 0.001) and median OS (43.5 months vs NR, p = 0.007) than those with IDH mutated grade III anaplastic astrocytoma and oligodendroglioma.
Trisomy of chromosome 7 in IDH mutated astrocytoma and PTEN mutations in IDH mutated oligodendroglioma are potential markers of poor prognosis, but require confirmation in larger series.
One hundred twenty-six tumors could be classified: 20 as type II (IDH mutation [mut], "astrocytoma"), 49 as type I (1p/19q codeletion, "oligodendroglioma"), 55 as type III (7+/10q- or TERTmut and 1p/19q intact, "glioblastoma"), and 2 as childhood glioblastoma (H3F3Amut), leaving 7 unclassified (total 91% classified).