====== Oligodendroglioma Classification ====== [[Oligodendroglioma IDH-mutant and 1p/19q-codeleted]] [[Oligodendroglioma NOS]] [[Anaplastic oligodendroglioma, IDH-mutant & 1p/19q-codeleted]] [[Anaplastic oligodendroglioma NOS]] ---- They can be classified by degree of malignancy into grade II and grade III, according to [[WHO classification]]. Only 30% of oligodendroglial tumors are [[anaplastic oligodendroglioma]]s [[Supratentorial oligodendroglioma]] [[Infratentorial oligodendroglioma]] [[Spinal oligodendroglioma]]. see [[Insular oligodendroglioma]]. ---- Combining histology and genetics in one diagnosis necessarily implicates the occurrence of occasional cases where genetics appears to contradict histology. No classification can encompass the totality of nature’s breadth and diversity. For example, true oligodendroglioma without IDH mutation and without 1p/19q co-deletion may exist in pediatric patients. These “pediatric-type oligodendrogliomas” are mentioned in the Blue Book ((Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2016) World Health Organization histological classification of tumours of the central nervous system. International Agency for Research on Cancer, Lyon)) ,but they are not part of the WHO Classification, and occurrence in adult patients remains unclear. ====RNA sequencing==== Tirosh et al., profile 4,347 single cells from six [[IDH1]] or [[IDH2]] mutant human oligodendrogliomas by [[RNA sequencing]] (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. The single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management ((Tirosh I, Venteicher AS, Hebert C, Escalante LE, Patel AP, Yizhak K, Fisher JM, Rodman C, Mount C, Filbin MG, Neftel C, Desai N, Nyman J, Izar B, Luo CC, Francis JM, Patel AA, Onozato ML, Riggi N, Livak KJ, Gennert D, Satija R, Nahed BV, Curry WT, Martuza RL, Mylvaganam R, Iafrate AJ, Frosch MP, Golub TR, Rivera MN, Getz G, Rozenblatt-Rosen O, Cahill DP, Monje M, Bernstein BE, Louis DN, Regev A, Suvà ML. Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma. Nature. 2016 Nov 2. doi: 10.1038/nature20123. [Epub ahead of print] PubMed PMID: 27806376. )). ===== Molecular subtypes ===== Wu et al. identified and independently validated two reproducible [[subtype]]s associated with distinct [[molecular]] characteristics and clinical outcomes. The proliferative subtype, named [[Oligo1]], was characterized by more tumors of CNS WHO grade 3, as well as worse prognosis compared to the [[Oligo2]] subtype. Besides the clinicopathologic features, Oligo1 exhibited enrichment of cell proliferation, regulation of cell cycle and [[Wnt]] [[signaling pathway]]s, and significantly altered genes, such as [[EGFR]], [[NOTCH1]] and [[MET]]. In contrast, Oligo2, with favorable outcome, presented increased activation of immune response and metabolic process. Higher T cell/APC co-inhibition and inhibitory checkpoint levels were observed in Oligo2 tumors. Finally, multivariable analysis revealed this classification was an independent prognostic factor in oligodendrogliomas, and the robustness of these molecular subgroups was verified in the validation cohorts ((Wu F, Yin YY, Fan WH, Zhai Y, Yu MC, Wang D, Pan CQ, Zhao Z, Li GZ, Zhang W. Immunological profiles of human oligodendrogliomas define two distinct molecular subtypes. EBioMedicine. 2022 Dec 14;87:104410. doi: 10.1016/j.ebiom.2022.104410. Epub ahead of print. PMID: 36525723; PMCID: PMC9772571.)). ===== Low-grade BRAF V600E mutant oligodendroglioma ===== [[Low-grade BRAF V600E mutant oligodendroglioma]].