伦敦大学学院大奥蒙德街儿童健康研究所Darren R. Hargrave小组取得一项新突破。他们的研究开发出了弥漫性中线胶质瘤的预后人脑网络。该研究于2026年6月10日发表于国际一流学术期刊《自然》杂志上。

该课题组研究人员开发了肿瘤网络映射来计算DMG的全脑连接概况，定义了一个与患者短期生存相关的跨脑桥和丘脑DMG的保守脑网络（DMG网络）。肿瘤与DMG网络的功能连接在两个外部验证队列中独立预测了患者的总生存期。肿瘤的生长映射到DMG网络特异性轨迹，网络内神经代谢变化的峰值在时空上与DMG的峰值年龄发生率一致。单核RNA测序数据分析证实了高连通性DMG中突触基因的多样性富集。引人注目的是，意外手术切除高连通性丘脑DMG组织赋予了显著的生存优势。总的来说，这些数据定义了DMG儿童中一个保守且具有预后重要性的大脑网络，这与DMG利用其他健康的大脑回路促进肿瘤生长的假设一致。

研究人员表示，弥漫性中线胶质瘤（DMGs）是儿童中枢神经系统几乎普遍致命的肿瘤。在动物模型中，DMG通过神经元到胶质瘤突触和胶质瘤到胶质瘤间隙连接偶联形成全脑整合网络。这种广泛的连通性通过旁分泌机制和直接的神经元-胶质瘤突触，有力地促进DMG和其他胶质恶性肿瘤的生长和侵袭。然而，这些连接在活人大脑中的组织和临床意义仍有待阐明。

附：英文原文

Title: A prognostic human brain network for diffuse midline glioma

Author: Sidpra, Jai, Lind, Valentina, Cohen, Alexander L., Schaper, Frederic L. W. V. J., Stone, Thomas J., Grabovska, Yura, Biswas, Asthik, Sudhakar, Sniya, Sepulveda, Francisco, Peres, Bruno S., Veronese, Greta, Alemn-Charlet, Cristina, Ogunbiyi, Olumide, Shamardani, Kiarash, Zhao, Jiaqi, Palacin, Alberto Castro, Miller, Gillian, Opipari, Raffaella S., De Vita, Enrico, Ridout, Deborah, Ferraciolli, Suely F., Lucato, Leandro T., Avsenik, Jernej, Piccirilli, Eleonora, Morales-La Madrid, Andrs, Muchart, Jordi, Ryan, Maura E., Patel, Rajan, Haldipur, Parthiv, Hill, Ciaran S., Krger, Marie T., Zrinzo, Ludvic, Jeelani, Noor ul Owase, Martinez-Barbera, Juan Pedro, Donson, Andrew M., Dorris, Kathleen, Morgan, Paul S., Mackay, Alan, Venkatesh, Humsa S., Horn, Andreas, Mueller, Sabine, Green, Adam L., Mirsky, David M., Akram, Harith, Jones, Chris, Aquilina, Kristian, Mankad, Kshitij, Monje, Michelle, Jacques, Thomas S., Fox, Michael D., Hargrave, Darren R.

Issue&Volume: 2026-06-10

Abstract: Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3,4,5,6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly promotes the growth and invasion of DMG3,4,5,6,7,8,9 and other glial malignancies10,11,12 through paracrine mechanisms and direct neuron-to-glioma synapses. However, the organization and clinical implications of these connections in the living human brain remain to be elucidated. Here, we develop tumour network mapping to compute the brain-wide connectivity profile of DMG, defining a conserved brain network across pontine and thalamic DMG associated with patient short-term survival (DMG network). Tumour functional connectivity with the DMG network was independently predictive of patient overall survival across two external validation cohorts. Tumour growth mapped to DMG network-specific trajectories and peak in-network neurometabolic changes across development spatiotemporally aligned with the peak age incidence of DMG. Analyses of single-nucleus RNA sequencing data confirmed diverse synaptic gene enrichment in high-connectivity DMG. Strikingly, incidental surgical resection of high-connectivity thalamic DMG tissue conferred a significant survival advantage. Collectively, these data define a conserved and prognostically important brain network in children with DMG, consistent with the hypothesis that DMGs exploit otherwise healthy brain circuits to promote tumour growth.

DOI: 10.1038/s41586-026-10631-3

Source: https://www.nature.com/articles/s41586-026-10631-3