Uncovering chromatin factor landscapes in head and neck squamous cell carcinoma

Chromatin factors, defined here as proteins that chemically modify the DNA and histones, remodel chromatin and regulate nucleosome occupancy, play central roles in the transcriptional regulation of genes and are implicated in cancer initiation and progression in multiple cancer types. To systematically investigate the genomic and expression alterations of chromatin factors in head and neck squamous cell carcinoma (HNSCC), we utilized the molecular profiles from 530 HNSCC tumor samples in the Cancer Genome Atlas (TCGA), and characterized the mutational, copy number and transcriptional alterations of 422 chromatin factors, as well as their correlation with the "cold" tumor phenotype in HPV-negative and HPV-positive HNSCC. Histone-lysine N-methyltransferase 2D (MLL2) was the most frequently mutated chromatin factor in both HPV-negative and HPV-positive HNSCC, with mutation frequencies of 12-17 %. Actin Like 6A (ACTL6A), a component of the SWI/SNF chromatin remodeling complex, was the most frequently copy-number amplified chromatin factor in both HPV-negative and HPV-positive HNSCC, with amplification frequencies of 19-24 %. Double PHD Fingers 1 (DPF1), a component of the chromatin remodeling complex, and Ubiquitin Like With PHD AndRing Finger Domains1 (UHRF1) were the most overexpressed chromatin factors in HPV-negative and HPV-positive HNSCC tumors respectively. Components of the chromatin remodeling complex, such as ACTL6A, SMARCA1 and MORF4L2, were correlated with the "cold" tumor phenotype in both HPV-negative and HPV-positive HNSCC. This brief study highlights epigenetic chromatin factors that may drive oncogenesis and immune evasion, thereby identifying novel targets for cancer therapy in clearly defined, epigenetically-driven subtypes of HPV-negative and HPV-positive HNSCC.