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Oncogenic Fusions Converge on Shared Mechanisms in Initiating Astroblastoma by Yixing Shi1,2,5, Qianqian Sun3,5, Fuchuan Jia3, Xiangyu Xie1,2, Xiangyu Zhou1,2, Rong Guo3, is a book available to read on EtoBox.

What is Oncogenic Fusions Converge on Shared Mechanisms in Initiating Astroblastoma about?

Chromosomal rearrangements and gene fusions are the initial events in the Check for updatesdevelopment of many cancers. Astroblastoma (ABM), a brain cancer of unknown cellular origin and challenging to treat, is associated with diverse in-frame gene fusions, including MN1-BEND2 and MN1-CXXC5 (refs. 1,2). However, it remains unclear whether these gene fusions contribute to tumorigenesis. Here we show in mice that these two ABM-associated fusions converge on similar molecular activities and initiate malignancy specifcally in ventral telencephalon neural progenitors. BEND2 and CXXC5 recognize similar DNA motifs, which indicates a convergence on downstream gene regulation. Expression of MN1-BEND2 in ventral telencephalon neural progenitors results in aberrant cell proliferation, impaired diferentiation, a perivascular occupancy pattern of cells reminiscent of ABM and acquisition of an ABM-associated transcriptional signature. By contrast, MN1-BEND2 expression in dorsal telencephalon neural progenitors leads to extensive cell death. This cell-type-specifc malignancy depends on OLIG2 expression. Mechanistically, both ABM-associated fusion proteins (MN1–BEND2 and MN1–CXXC5) induce overlap

Author

Yixing Shi1,2,5, Qianqian Sun3,5, Fuchuan Jia3, Xiangyu Xie1,2, Xiangyu Zhou1,2, Rong Guo3,

Published

2025

Language

EN