5-Hydroxymethylation highlights the heterogeneity in keratinization and cell junctions in head and neck cancers.

Clinical Epigenetics
Siyu LiuMaureen A Sartor

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide, with human papillomavirus (HPV)-related HNSCC rising to concerning levels. Extensive clinical, genetic and epigenetic differences exist between HPV-associated HNSCC and HPV-negative HNSCC, which is often linked to tobacco use. However, 5-hydroxymethylation (5hmC), an oxidative derivative of DNA methylation and its heterogeneity among HNSCC subtypes, has not been studied. We characterized genome-wide 5hmC profiles in HNSCC by HPV status and subtype in 18 HPV(+) and 18 HPV(-) well-characterized tumors. Results showed significant genome-wide hyper-5hmC in HPV(-) tumors, with both promoter and enhancer 5hmC able to distinguish meaningful tumor subgroups. We identified specific genes whose differential expression by HPV status is driven by differential hydroxymethylation. CDKN2A (p16), used as a key biomarker for HPV status, exhibited the most extensive hyper-5hmC in HPV(+) tumors, while HPV(-) tumors showed hyper-5hmC in CDH13, TIMP2, MMP2 and other cancer-related genes. Among the previously reported two HPV(+) subtypes, IMU (stronger immune response) and KRT (more keratinization), the IMU subtype revealed hyper-5hmC and up-regulation of gen...Continue Reading

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Methods Mentioned

BETA
immunoprecipitation
RNA-seq
ChIP-seq
hMeDIP-seq
PCR

Software Mentioned

PePr
R
DESeq2
bowtie2
FastQC
MACS2
Bioconductor package
ChromHMM
HOMER
bedtools

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