Glioblastoma, the predominant adult malignant brain tumor, has been computationally classified into molecular subtypes whose functional relevance remains to be comprehensively established. Tumors from genetically engineered glioblastoma mouse models initiated by identical driver mutations in distinct cells of origin portray unique transcriptional profiles reflective of their respective lineage. Here, we identify corresponding transcriptional profiles in human glioblastoma and describe patient-derived xenografts with species-conserved subtype-discriminating functional properties. The oligodendrocyte lineage-associated glioblastoma subtype requires functional ERBB3 and harbors unique therapeutic sensitivities. These results highlight the importance of cell lineage in glioblastoma independent of driver mutations and provide a methodology for functional glioblastoma classification for future clinical investigations.

胶质母细胞瘤是主要的成人恶性脑肿瘤，已通过计算分类为分子亚型，其功能相关性仍有待全面确定。由不同起源细胞中的相同驱动突变引发的基因工程胶质母细胞瘤小鼠模型的肿瘤描绘了反映其各自谱系的独特转录谱。在这里，我们确定了人类胶质母细胞瘤中相应的转录谱，并描述了具有物种保守亚型区分功能特性的患者来源的异种移植物。少突胶质细胞谱系相关的胶质母细胞瘤亚型需要功能性 ERBB3 并具有独特的治疗敏感性。