FOXA1

This study investigates how altered enhancers in prostate cancer cooperate within the 3D chromatin architecture to drive oncogenic programs. Researchers identified prostate cancer-specific enhancers that form highly nested interactions with promoters, coalescing into multi-connected hubs. CRISPR/Cas9 perturbations distinguished distinct enhancer classes: central enhancers, whose deletion collapses hub-wide activity and impairs cell proliferation, and redundant enhancers, whose deletion has minimal impact due to compensatory architectural rewiring. The transcription factor FOXA1 was found to directly bind and regulate these distinct enhancer classes. These findings suggest that enhancers function in a coordinated manner and open new avenues for precision therapies.

Somatic mutations in GC-rich promoter regions are significant drivers of cancer, yet their detection is challenging due to poor sequencing coverage in these areas. This study introduces a hybrid capture assay optimized for over 3000 cancer gene promoters, enabling deep sequencing of these complex regions. This method facilitates the discovery of reliable point mutations, short insertions/deletions, copy number variants, and mutational signatures. The assay nominated candidate noncoding driver mutations in CDK4, SMAD3, and GATA3 in breast cancer, paving the way for future functional follow-up.