A population-based analysis of the molecular landscape of glioma in adolescents and young adults reveals insights into gliomagenesis
Gliomas are a major cause of cancer-related deaths in adolescents and young adults (AYAs; ages 15–39 years). Different molecular alterations drive gliomas in children and adults, leading to distinct biology and clinical consequences, but the implications of pediatric- versus adult-type alterations in AYAs are unknown. Our population-based analysis of 1,456 clinically and molecularly characterized gliomas in patients aged 0–39 years addresses this gap. Pediatric-type alterations were found in 31% of AYA gliomas and conferred superior outcomes compared to adult-type alterations. AYA low-grade gliomas with specific RAS–MAPK alterations exhibited senescence, tended to arise in different locations and were associated with superior outcomes compared to gliomas in children, suggesting different cellular origins. Hemispheric IDH-mutant, BRAF p.V600E and FGFR-altered gliomas were associated with the risk of malignant transformation, having worse outcomes with increased age. These insights into gliomagenesis may provide a rationale for earlier intervention for certain tumors to disrupt the typical behavior, leading to improved outcomes.
胶质母细胞瘤是青少年和年轻人（AYAs，年龄15-39岁）癌症死亡的主要原因。不同类型的分子改变驱动了儿童和成年患者的胶质母细胞瘤，导致其生物性和临床后果不同，但针对青少年中的儿童型和成人型变异的隐式影响尚不明确。我们对0至39岁临床和分子特征明确的1456例胶质母细胞瘤的总体分析填补了这一空白。儿童型改变占AYA胶质母细胞瘤的31%，相比成人型改变了更优的结果。具有特定RAS-MAPK信号通路突变的低级Grade AYA胶质母细胞瘤表现出衰老特征，倾向于发生于不同的部位，并与较好的结果相关联，这表明这些肿瘤来源于不同的细胞起源。半球性IDH突变体、BRAF p.V600E突变和FGFR-突变的胶质母细胞瘤与恶性转化的风险有关，在年龄增长的情况下风险更大。这些对胶质母细胞瘤发生机制的理解可能为某些肿瘤提供 rationale 以更早干预，从而破坏其典型行为模式，提高治疗效果。
肿瘤(癌症)患者之家