IDH‐mutated astrocytomas with 19q‐loss constitute a subgroup that confers better prognosis

Abstract

IDH‐mutant gliomas are classified into astrocytic or oligodendroglial tumors by 1p/19q status in the WHO 2016 classification, with the latter presenting with characteristic morphology and better prognosis in general. However, the morphological and genetic features within each category are varied, and there might be distinguishable subtypes. We analyzed 170 WHO grade II‐IV gliomas resected in our institution. 1p/19q status was analyzed by microsatellite analysis, and genetic mutations were analyzed by next‐generation sequencing and Sanger sequencing. For validation, the Brain Lower Grade Glioma dataset of The Cancer Genome Atlas was analyzed. Of the 42 grade III IDH‐mutated gliomas, 12 were 1p‐intact/19q‐intact (anaplastic astrocytomas [AA]), 7 were 1p‐intact/19q‐loss (AA), and 23 showed 1p/19q‐codeletion (anaplastic oligodendrogliomas). Of the 88 IDH‐wild type glioblastomas (GBMs), 14 showed 1p‐intact/19q‐loss status. All of the seven 1p‐intact/19q‐loss AAs harbored TP53 mutation, but no TERT promotor mutation. All 19q‐loss AAs had regions presenting oligodendroglioma‐like morphology, and were associated with significantly longer overall survival compared to 19q‐intact AAs (P = .001). This tendency was observed in The Cancer Genome Atlas Lower Grade Glioma dataset. In contrast, there was no difference in overall survival between the 19q‐loss GBM and 19q‐intact GBM (P = .4). In a case of 19q‐loss AA, both oligodendroglial morphology and 19q‐loss disappeared after recurrence, possibly indicating correlation between 19q‐loss and oligodendroglial morphology. We showed that there was a subgroup, although small, of IDH‐mutated astrocytomas harboring 19q‐loss that present oligodendroglial morphology, and also were associated with significantly better prognosis compared to other 19q‐intact astrocytomas.

Molecular profiles of BRCA1‐associated ovarian cancer treated by platinum‐based therapy: Analysis of primary, residual and relapsed tumors

“…OC86 carried PTCH1 mutation (Fig. 21 Six OCs included in our study carried 1p/19q co-deletion, as determined by NGS; the presence of this co-deletion was validated by appropriate PCR assay in five of these cases (Supplementary Information Tables S4 and S5). PTCH1 inactivation is frequently observed in basal cell carcinomas.…”

“…Combination of IDH2 mutation and 1p/19q co-deletion is characteristics for glioblastoma, although distinct hotspots for IDH1/2 amino acid substitutions are observed in brain tumors. 21 Six OCs included in our study carried 1p/19q co-deletion, as determined by NGS; the presence of this co-deletion was validated by appropriate PCR assay in five of these cases (Supplementary Information Tables S4 and S5). Some IDH2-mutated proteins, IDH2 p. R140Q, p.R172S and p.R172K, can be targeted by enasidenib, which has already been approved for the treatment of acute myeloid leukemia.…”

The T2-FLAIR–mismatch sign as an imaging biomarker for IDH and 1p/19q status in diffuse low-grade gliomas: a systematic review with a Bayesian approach to evaluation of diagnostic test performance

“…The presence of both IDH mutation and 1p/19q codeletion is associated with a more favorable clinical course, with improved sensitivity to procarbazine, lomustine, and vincristine chemotherapy and longer survival. 5,22,27 Therefore, a molecular classification might capture clinical behavior and prognosis more accurately than traditional histopathologic characteristics. 3 Consequently, due to the revised 2016 WHO classification of diffuse…”

SMPD3-mediated extracellular vesicle biogenesis inhibits oligodendroglioma growth

“…5D). We further dissected the lower-grade glioma dataset into IDH-mutant astrocytoma and IDH-mutant ODG and found that astrocytoma patients, which have a shorter survival time (median survival=9-13 years 6,36 ), presented with lower SMPD3 transcript levels compared to ODG patients, which have a longer survival time (median survival= 12-14 years 40,41 ; Fig. 5E; p<0.0001) -suggesting that higher SMPD3 levels may reduce tumor growth.…”

“…The most aggressive and most frequently studied is glioblastoma multiforme (GBM), a high-grade astrocytoma with 5-year survival rates of less than 5% 5 . In contrast, lower-grade gliomas (World Health Organization-WHO stage II/III tumors), which include oligodendroglioma (ODG), are slower growing tumors, with median survival times between 9-14 years 6 . Glioma subtypes each have a unique constellation of mutations, that in ODG typically includes isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations, chromosomal 1p/19q co-deletion, and mutation of Capicua (CIC), a transcriptional repressor, in the retained 19q allele 7,8,9,10 .…”