Pediatric Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland; Department of Pediatrics, McGill University, Montreal, Quebec, Canada; Université Paris-Saclay & Gustave Roussy Unité Mixte de Recherche 8203 du Centre National de la Recherche Scientifique & Departement de Cancerologie de l'Enfant et de l'Adolescent, Villejuif, France.
Neuro Oncol. 2017 Aug 1;19(8):1025-1034. doi: 10.1093/neuonc/nox021.
Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies have been undertaken-all of which have had a negligible impact on the natural history of this disease. More recently, improvements in neurosurgical techniques have allowed for the safe upfront biopsy of DIPG, which, together with a wider use of autopsy tissue, has led to an evolving understanding of the biology of this tumor. The discovery of a recurrent somatic gain-of-function mutation leading to lysine 27 to methionine (p.Lys27Met, K27M) substitution in histone 3 variants characterizes more than 85% of DIPG, suggesting for the first time the role of the epigenome and histones in the pathogenesis of this disease, and more unified diagnostic criteria. Along with further molecular insights into the pathogenesis of DIPG, rational targets are being identified and studied in the hopes of improving the otherwise dismal outcome for children with DIPG.
弥漫性内在脑桥神经胶质瘤（DIPG）已被证明是所有儿科癌症中最具挑战性的一种。由于历史上对获取肿瘤组织进行研究的保守态度，并且基于 DIPG 的生物学将反映幕上高级别星形细胞瘤的生物学的错误假设，已经进行了无数的研究 - 所有这些研究都对这种疾病的自然史几乎没有影响。最近，神经外科技术的改进使得 DIPG 的安全 upfront 活检成为可能，再加上尸检组织的更广泛使用，导致人们对这种肿瘤的生物学有了不断发展的认识。在组蛋白变体中发现了导致赖氨酸 27 到蛋氨酸（p.Lys27Met，K27M）取代的反复出现的体细胞获得性功能突变，这一发现超过了 85％的 DIPG，这表明首次发挥了表观基因组和组蛋白在这种疾病发病机制中的作用，以及更统一的诊断标准。随着对 DIPG 发病机制的进一步分子研究，正在确定和研究合理的靶标，以期改善 DIPG 儿童的预后。
