HOXD12 defines an age-related aggressive subtype of oligodendroglioma.

Oligodendroglioma, IDH-mutant and 1p/19q-codeleted has highly variable outcomes that are strongly influenced by patient age. The distribution of oligodendroglioma age is non-Gaussian and reportedly bimodal, which motivated our investigation of age-associated molecular alterations that may drive poorer outcomes. We found that elevated HOXD12 expression was associated with both older patient age and shorter survival in the TCGA (FDR < 0.01, FDR = 1e-5) and the CGGA (p = 0.03, p < 1e-3). HOXD12 gene body hypermethylation was associated with older age, higher WHO grade, and shorter survival in the TCGA (p < 1e-6, p < 0.001, p < 1e-3) and with older age and higher WHO grade in Capper et al. (p < 0.002, p = 0.014). In the TCGA, HOXD12 gene body hypermethylation and elevated expression were independently prognostic of NOTCH1 and PIK3CA mutations, loss of 15q, MYC activation, and standard histopathological features. Single-nucleus RNA and ATAC sequencing data showed that HOXD12 activity was elevated in neoplastic tissue, particularly within cycling and OPC-like cells, and was associated with a stem-like phenotype. A pan-HOX DNA methylation analysis revealed an age and survival-associated HOX-high signature that was tightly associated with HOXD12 gene body methylation. Overall, HOXD12 expression and gene body hypermethylation were associated with an older, atypically aggressive subtype of oligodendroglioma.

Nuechterlein N ，Cimino S ，Shelbourn A ，Ha V ，Arora S ，Rajan S ，Shapiro LG ，Holland EC ，Aldape K ，McGranahan T ，Gilbert MR ，Cimino PJ ... -  《-》

Ki-67 and MCM6 labeling indices are correlated with overall survival in anaplastic oligodendroglioma, IDH1-mutant and 1p/19q-codeleted: a multicenter study from the French POLA network.

Anaplastic oligodendroglioma (AO), IDH-mutant and 1p/19q codeleted (IDHmut+/1p19qcodel), is a high-grade glioma with only limited prognostic markers. The primary objective of this study was to evaluate, by immunohistochemistry, the prognostic value of two proliferation markers, MCM6 and Ki-67, in a large series of IDHmut+/1p19qcodel AO included in the POLA ("Prise en charge des Oligodendrogliomes Anaplasiques") French national multicenter network. We additionally examined the transcriptome obtained from this series to understand the functional pathways dysregulated with the mRNA overexpression of these two markers. The labeling indices (LI) of MCM6 and Ki-67 were obtained via computer-assisted color image analyses on immunostained AO tissues of the cohort (n = 220). Furthermore, a subgroup of AO (n = 68/220) was used to perform transcriptomic analyses. A high LI of either MCM6 (≥50%) or Ki-67 (≥15%) correlated with shorter overall survival, both in univariate (P = 0.013 and P = 0.004, respectively) and multivariate analyses (P = 0.027; multivariate Cox model including age, mitotic index, MCM6 and Ki-67). MCM6 and Ki-67 LI also correlated with overall survival in an additional retrospective cohort of 30 grade II IDHmut+/1p19qcodel oligodendrogliomas. The prognostic value of MCM6 mRNA level was confirmed in The Cancer Genome Atlas (TCGA) IDHmut+/1p19qcodel gliomas. The transcriptomic approach revealed that high transcriptional expressions of MCM6 and MKI67 were both linked positively with cell cycle progression, DNA replication, mitosis, pro-neural phenotype as well as neurogenesis, and negatively with microglial cell activation, immune response, positive regulation of myelination, oligodendrocyte development, beta-amyloid binding and postsynaptic specialization. In conclusion, the overexpression of MCM6 and/or Ki-67 is independently associated to shorter overall survival in IDHmut+/1p19qcodel AO. These two easy-to-use and cost-effective markers could thus be used concurrently in routine pathology practice. Additionally, the transcriptomic analyses showed that AO with high proliferation index have down-regulated immune response and lower microglial cells activation, and bears pro-neural phenotype.

Pouget C ，Hergalant S ，Lardenois E ，Lacomme S ，Houlgatte R ，Carpentier C ，Dehais C ，Rech F ，Taillandier L ，Sanson M ，Appay R ，Colin C ，Figarella-Branger D ，Battaglia-Hsu SF ，Gauchotte G ... -  《-》

Contrast enhancement in 1p/19q-codeleted anaplastic oligodendrogliomas is associated with 9p loss, genomic instability, and angiogenic gene expression.

Reyes-Botero G ，Dehais C ，Idbaih A ，Martin-Duverneuil N ，Lahutte M ，Carpentier C ，Letouzé E ，Chinot O ，Loiseau H ，Honnorat J ，Ramirez C ，Moyal E ，Figarella-Branger D ，Ducray F ，POLA Network ... -  《-》

Gliosarcoma arising from oligodendroglioma, IDH mutant and 1p/19q codeleted.

Herein, we present a rare case of gliosarcoma arising from oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted. A 36-year-old man presented with a non-enhanced calcified abnormal lesion on the right frontal lobe. The patient underwent subtotal surgical resection, PAV chemotherapy (procarbazine, nimustine (ACNU) and vincristine), and fractionated radiotherapy with 50 Gy. The pathological diagnosis was oligodendroglioma, IDH mutant and 1p/19q codeleted, World Health Organization 2016 grade II. Six years later, a new enhanced lesion appeared, and the recurrent tumor was surgically removed. Although the histopathological findings indicated gliosarcoma, the recurrent tumor still demonstrated the IDH mutation and 1p/19q codeleted. Thus, the recurrent tumor was considered to originate from oligodendroglioma, rather than being newly generated after chemoradiotherapy. Interestingly, the second recurrent tumor responded well to temozolomide chemotherapy. Based on the findings of this case, oligodendrogliomas have the potential for mesenchymal transformation on progression, while keeping their genotype.

Yasuda T ，Nitta M ，Komori T ，Kobayashi T ，Masui K ，Maruyama T ，Sawada T ，Muragaki Y ，Kawamata T ... -  《-》

Somatostatin receptor 2A protein expression characterizes anaplastic oligodendrogliomas with favorable outcome.

Appay R ，Tabouret E ，Touat M ，Carpentier C ，Colin C ，Ducray F ，Idbaih A ，Mokhtari K ，Uro-Coste E ，Dehais C ，Figarella-Branger D ，POLA network ... -  《Acta Neuropathologica Communications》