From Enhancers to Keratinocyte Cancers

Abstract

Epigenetic dysregulation and disruption of gene enhancer networks are both pervasive in human cancers, and yet, their roles in keratinocyte cancers are poorly understood. Utilizing patient samples, Yao et al. (2020) provide an initial framework for understanding the underlying mechanisms by integrating enhancer and transcriptional alterations that occur during the progression of basal cell and squamous cell carcinomas.

Figure 1.. Enhancer chromatin accessibility can determine whether a gene is transcriptionally active or repressed.

Dysregulation of these processes may be a key driver of KC cancers such as BCC and SCC. The authors mapped H3K27ac, a modification associated with active enhancers, in human patient samples to gain insights into epigenetic contributions to these ubiquitous cancers. In the case of BCC, aberrant enhancer activation is associated with developmental pathways and is enriched for transcription factor motifs such as SMAD3 and/or SMAD4, FGFR2, and FOSL2. In SCC, altered enhancers are enriched for immune-related pathways and display gains in ETS1, FOXP3, RUNX1, and NF-κB/Rel transcription factor sites along with a loss of H3K27ac enrichment and/or enhancer activity at retinoid-related transcription factor motifs. AP-1, activator protein-1; BCC, basal cell carcinoma; FGF, fibroblast GF; H3K27ac, acetylated histone H3 lysine 27; KC, keratinocyte; SCC, squamous cell carcinoma.