Résumé
Background: The life expectancy of patients with diffuse IDH-mutant low-grade gliomas (IDHmt LGG) ranges from 5 to over 20 years. Tumor behavior, including spontaneous growth rate, varies even within homogeneously classified subtypes of oligodendroglioma and astrocytoma. Risk-adjusted treatment strategies are needed to avoid therapy-related toxicities, without compromising outcome. The spontaneous tumor volume growth rate (TVGR) serves as a prognostic marker and predicts response to therapy. Accurate prediction of TVGR through biomarkers would enable an improved evidence-based risk management.Patients & methods: A cohort of 77 patients treated in Montpellier, France, for IDHmt LGG grade II (WHO 2016) (29 oligodendrogliomas, 48 astrocytomas) was constituted (age >18 years; MRI scans, frozen tumor tissue). The DNA methylome (Illumina, EPIC array) and transcriptome (RNAseq) were established. TVGR was determined based on serial MRIs collected over the "watch & wait" period before first treatment beyond surgery. Transcriptomic and methylome data were analyzed for signatures associated with TVGR using rank-rank regression followed by preranked gene set enrichment analysis.Results: : The median TVGR was lower in IDHmt codeleted compared to non-codeleted LGG, (0.241 year-1 range 0.082-0.366 vs 0.424 year-1 range 0.264-0.609, p < 0.001). In codeleted IDHmt LGG, TVGR was associated with upregulated gene signatures for neuronal systems, synaptic activity, and activation of repressed or poised signatures of neural progenitor cells; while the TVGR in non-codeleted IDHmt LGG was dominanted by upregulated proliferation-related signatures, including DNA replication and repair.Conclusion: Spontaneous TVGR of codeleted and non-codeleted IDHmt LGG involve distinct biological processes, suggesting possible differences in response to therapies.