协和医学院最新Nature论文：揭开这种致命脑肿瘤的细胞起源和发病机制

Core Insights - Astroblastoma (ABM) is a rare central nervous system tumor primarily affecting young females, characterized by high local recurrence rates and often misdiagnosed due to overlapping features with other brain tumors [2][4] - Recent research published in Nature reveals the cellular origins and molecular mechanisms of ABM, providing new insights for targeted therapies [3][8] Genetic Characteristics - The majority of ABM cases (approximately 92%) exhibit significant genetic fusions, particularly MN1-BEND2 and MN1-CXXC5, which involve the MN1 gene's first exon fusing with the 3' end of BEND2 or CXXC5 genes [2][4] - Other less common fusions include EWSR1-BEND2, MAMLD1-BEND2, and TCF3-BEND2, indicating a complex genetic landscape [2] Mechanistic Insights - Mouse experiments demonstrate that MN1-BEND2 and MN1-CXXC5 fusion proteins exhibit consistent molecular activities, specifically inducing malignancy in ventral brain neural progenitor cells [5][7] - These fusion proteins activate overlapping transcriptional responses, including the PDGFRα pathway, which serves as a potential therapeutic target [5][7] Implications for Treatment - The study suggests that different fusion genes lead to functionally similar fusion transcription factors that hijack developmental regulatory mechanisms, indicating a convergent evolution in tumorigenesis [8] - The findings clarify the cellular origins of ABM and open avenues for developing targeted treatments against this challenging tumor type [3][8]