Oncogenes articles from across Nature Portfolio

Primary mismatch repair-deficient gliomas are hypermutant but molecularly heterogeneous cancers with poor prognosis. We show that non-random mutational signatures cause somatic mutations in key glioma drivers that define genetic subgroups of this disease. Each subgroup harbors distinct mechanisms of genomic instability that shape their biological behaviors and immunotherapy responses.

Our study showed that lineage-determining transcription factors, such as EBF1 in B cell lymphoma and TCF1 in T cell leukaemia, shape 3D genome architecture by constraining cohesin movement. Cohesin in turn positions enhancers at the spatial centres of oncogenic loci and enables multi-enhancer regulation of key oncogenes. Together, these findings identify a unifying mechanism that links transcription factor activity, chromatin topology and oncogene control.