Landscape of enhancer disruption and functional screen in melanoma. Landscape of enhancer disruption and functional screen in melanoma

Here, we leveraged 297 melanoma whole-genome sequencing (WGS) samples to prioritize highly recurrent regions (HRRs). By performing a genome-scale CRISPR interference (CRISPRi) screen on HRR-associated enhancers in melanoma cells, we identified 66 significant hits which could have tumor-suppressive roles. These functional enhancers show unique mutational patterns independent of classical significantly mutated genes in melanoma. Target gene analysis for the essential enhancers revealed many known and hidden mechanisms underlying melanoma growth. Utilizing extensive functional validation experiments, we demonstrated that a super enhancer element could modulate melanoma cell proliferation by targeting MEF2A and another distal enhancer was able to sustain PTEN tumor-suppressive potential via long-range interaction. Overall design: Refer to individual Series