Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

IF 16.4 1区医学 Q1 CLINICAL NEUROLOGY Neuro-oncology Pub Date : 2024-09-05 DOI:10.1093/neuonc/noae080

Gunther Nussbaumer, Martin Benesch, Yura Grabovska, Alan Mackay, David Castel, Jacques Grill, Marta M Alonso, Manila Antonelli, Simon Bailey, Joshua N Baugh, Veronica Biassoni, Mirjam Blattner-Johnson, Alberto Broniscer, Andrea Carai, Giovanna Stefania Colafati, Niclas Colditz, Selim Corbacioglu, Shauna Crampsie, Natacha Entz-Werle, Matthias Eyrich, Lea L Friker, Michael C Frühwald, Maria Luisa Garrè, Nicolas U Gerber, Felice Giangaspero, Maria J Gil-da-Costa, Norbert Graf, Darren Hargrave, Peter Hauser, Ulrich Herrlinger, Marion Hoffmann, Esther Hulleman, Elisa Izquierdo, Sandra Jacobs, Michael Karremann, Antonis Kattamis, Rejin Kebudi, Rolf-Dieter Kortmann, Robert Kwiecien, Maura Massimino, Angela Mastronuzzi, Evelina Miele, Giovanni Morana, Claudia M Noack, Virve Pentikainen, Thomas Perwein, Stefan M Pfister, Torsten Pietsch, Kleoniki Roka, Sabrina Rossi, Stefan Rutkowski, Elisabetta Schiavello, Clemens Seidel, Jaroslav Štěrba, Dominik Sturm, David Sumerauer, Anna Tacke, Sara Temelso, Chiara Valentini, Dannis van Vuurden, Pascale Varlet, Sophie E M Veldhuijzen van Zanten, Maria Vinci, André O von Bueren, Monika Warmuth-Metz, Pieter Wesseling, Maria Wiese, Johannes E A Wolff, Josef Zamecnik, Andrés Morales La Madrid, Brigitte Bison, Gerrit H Gielen, David T W Jones, Chris Jones, Christof M Kramm

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Abstract

Background: The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established.

Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization.

Results: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-year survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n = 49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wild-type (n = 31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n = 19), pedHGG_A/B (n = 6), and pedHGG_MYCN (n = 5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wild-type subgroup, recurrent alterations in EGFR (n = 10) and BCOR (n = 9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wild-type subgroup TP53 alterations had a significant negative effect on OS.

Conclusions: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).

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儿童脑胶质瘤病：具有独特分子特征的弥漫性胶质瘤预后不良表型。

背景：脑胶质瘤病（Gliomatosis cerebri，GC）是一种由放射学定义的高度浸润性弥漫性胶质瘤，由于与GC相关的分子特征尚未确定，该术语已被放弃：我们对104名患有GC的儿童和青少年进行了一项跨国回顾性研究，提供了全面的临床和（外）遗传特征：中位总生存期（OS）为 15.5 个月（四分位间范围为 10.9-27.7），2 年生存率为 28%。组织病理学分级与中位生存期显著相关：中枢神经系统 WHO II 级：47.8 个月（25.2-55.7）；III 级：15.9 个月（11.4-26.3）；IV 级：10.4 个月（8.8-14.4）。通过DNA甲基化分析（n=49），大多数肿瘤被归类为儿科型弥漫性高级别胶质瘤（pedHGG），H3-/IDH-野生型（n=31/49，63.3%），其中有pedHGG_RTK2（n=19）、pedHGG_A/B（n=6）和pedHGG_MYCN（n=5）等富集亚类，但只有一例pedHGG_RTK1。在 pedHGG、H3-/IDH-野生型亚组中，发现了表皮生长因子受体（EGFR）（n=10）和 BCOR（n=9）的反复改变。此外，我们还在16/49个肿瘤（32.7%）中观察到6号染色体的结构畸变。在pedHGG、H3-/IDH-野生型亚组中，TP53改变对OS有显著的负面影响：与之前的研究相反，我们这项具有代表性的儿科 GC 研究提供了证据，证明 GC 有很强的倾向性，即在特定分子特征（尤其是 pedHGG_RTK2、pedHGG_A/B、表皮生长因子受体和 BCOR 突变、6 号染色体重排）的背景下发生。

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来源期刊

Neuro-oncology 医学-临床神经学

CiteScore

27.20

自引率

6.30%

发文量

1434

审稿时长

3-8 weeks

期刊介绍： Neuro-Oncology, the official journal of the Society for Neuro-Oncology, has been published monthly since January 2010. Affiliated with the Japan Society for Neuro-Oncology and the European Association of Neuro-Oncology, it is a global leader in the field. The journal is committed to swiftly disseminating high-quality information across all areas of neuro-oncology. It features peer-reviewed articles, reviews, symposia on various topics, abstracts from annual meetings, and updates from neuro-oncology societies worldwide.