在早期儿童的声波刺猬(SHH)激活的结缔组织增生性/结节性髓母细胞瘤 (DMB)或伴有广泛结节的髓母细胞瘤 (MBEN)中，评估了临床危险因素和DNA甲基化模式对预后的影响，以更好地识别高风险复发患者。评估了144名年龄<5岁、接受节省放射治疗方法，包括132名患者接受脑室内甲氨蝶呤治疗的DMB(n=99)或MBEN(n=45)患者。DMB患者的5年无进展生存率不及MBEN(5年无进展生存率，71%[DMB] vs 93%[MBEN])。患者年龄>3岁与5年无进展生存率不利相关(>3岁: 47% vs <1岁: 85% vs 1-3岁: 84%)。根据2021年WHO分类，将该研究中可获得的DNA甲基化谱分类为SHH-1 (n=39)、SHH-2 (n=38)和SHH-3 (n=1)。SHH-2中的层次聚类确定了两个亚组：SHH-2a (n=19)和SHH-2b (n=19)。SHH-2b髓母细胞瘤患者年龄较大，主要表现为DMB组织学类型，并且更常位于小脑半球。SHH-2b中，染色体9q的缺失更为频繁，而SHH-2a中观察到的染色体改变较少。SHH-2b髓母细胞瘤患者的复发风险显著增加(5年无进展生存率：SHH-2b 58% vs SHH-1 83% vs SHH-2a 95%)。使用两个独立的队列(共n=188)确认SHH-2的亚型划分与关键临床和细胞遗传特征。基因突变分析显示，SHH-2a与SMO突变呈正相关。这些数据表明，早期儿童SHH-DMB/MBEN中存在更多的异质性：SHH-2分为一个MBEN组织学类型富集，SMO基因突变风险极低的SHH-2a亚组，和一个包括年龄较大、DMB患者且复发风险更高的SHH-2b亚组。©作者(s)2023年版权所有，由牛津大学出版社代表神经肿瘤学会发表。保留所有权利。如需权限，请发送电子邮件至: journals.permissions@oup.com。

The prognostic impact of clinical risk factors and DNA methylation patterns in sonic hedgehog (SHH)-activated early childhood desmoplastic/nodular medulloblastoma (DMB) or medulloblastoma with extensive nodularity (MBEN) were evaluated to better identify patients at risk for relapse.Hundred-forty-four patients with DMB (n=99) or MBEN (n=45) aged <5 years and treated with radiation-sparing approaches, including intraventricular methotrexate in 132 patients, were evaluated.Patients with DMB had less favorable 5-year progression-free survival than MBEN (5y-PFS, 71% [DMB] vs 93% [MBEN]). Patients' age >3 years was associated with more unfavorable 5y-PFS (47% [>3 years] vs 85% [<1 year] vs 84% [1-3 years]). DNA methylation profiles available (n=78) were reclassified according to the 2021 WHO classification into SHH-1 (n=39), SHH-2 (n=38), and SHH-3 (n=1). Hierarchical clustering delineated two subgroups among SHH-2: SHH-2a (n=19) and SHH-2b (n=19). Patients with SHH-2b medulloblastoma were older, predominantly displayed DMB histology, and were more often located in the cerebellar hemispheres. Chromosome 9q losses were more frequent in SHH-2b, while few chromosomal alterations were observed in SHH-2a. SHH-2b medulloblastoma carried a significantly increased relapse risk (5y-PFS: 58% [SHH-2b] vs 83% [SHH-1] vs 95% [SHH-2a]). Subclassification of SHH-2 with key clinical and cytogenetic characteristics was confirmed using two independent cohorts (total n=188). Gene mutation analysis revealed a correlation of SHH-2a with SMO mutations.These data suggest further heterogeneity within early childhood SHH-DMB/MBEN: SHH-2 splits into a very low-risk group SHH-2a enriched for MBEN histology and SMO mutations, and SHH-2b comprising older DMB patients with higher risk of relapse.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.