Huchedé Paul, Leblond Pierre, Castets Marie
Childhood Cancers & Cell Death (C3), Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Labex DevWeCan, Centre de Recherche en Cancérologie de Lyon (CRCL), 69008 Lyon, France.
Department of Pediatric Oncology, Institut d'Hematologie et d'Oncologie Pédiatrique, Centre Léon Bérard, 69008 Lyon, France.
Biomedicines. 2022 Jun 3;10(6):1311. doi: 10.3390/biomedicines10061311.
Pediatric high-grade gliomas (pHGGs) are a deadly and heterogenous subgroup of gliomas for which the development of innovative treatments is urgent. Advances in high-throughput molecular techniques have shed light on key epigenetic components of these diseases, such as K27M and G34R/V mutations on histone 3. However, modification of DNA compaction is not sufficient by itself to drive those tumors. Here, we review molecular specificities of pHGGs subcategories in the context of epigenomic rewiring caused by H3 mutations and the subsequent oncogenic interplay with transcriptional signaling pathways co-opted from developmental programs that ultimately leads to gliomagenesis. Understanding how transcriptional and epigenetic alterations synergize in each cellular context in these tumors could allow the identification of new Achilles' heels, thereby highlighting new levers to improve their therapeutic management.
儿童高级别胶质瘤（pHGGs）是一类致命且异质性的胶质瘤亚群，急需开发创新疗法。高通量分子技术的进展揭示了这些疾病的关键表观遗传成分，如组蛋白3上的K27M和G34R/V突变。然而，DNA压缩的改变本身不足以驱动这些肿瘤。在此，我们在由H3突变引起的表观基因组重排以及随后与从发育程序中借用的转录信号通路的致癌相互作用的背景下，综述pHGGs亚类的分子特异性，这种相互作用最终导致胶质瘤发生。了解转录和表观遗传改变如何在这些肿瘤的每个细胞环境中协同作用，可能有助于识别新的致命弱点，从而突出改善其治疗管理的新方法。
