American Association for Cancer Research
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FIGURE 3 from Whole-genome CpG-resolution DNA Methylation Profiling of HNSCC Reveals Distinct Mechanisms of Carcinogenesis for Fine-scale HPV+ Cancer Subtypes

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posted on 2023-08-30, 14:20 authored by Tingting Qin, Shiting Li, Leanne E. Henry, Elysia Chou, Raymond G. Cavalcante, Bailey F. Garb, Nisha J. D'Silva, Laura S. Rozek, Maureen A. Sartor

DNA methylation-based gene set enrichment captures gene expression-based pathway-level differences. A, Dotplot for top 40 significant RNA enrichment terms, colored by −log10(P-value) illustrating enrichment results from RNA, DMRs across the whole genome, <5 kb from TSS, exons, and introns. B, Scatter plot for directional RNA and DNA methylation enrichment test results. Right quadrants represent significantly hypermethylated GO terms in IMU; top quadrants represent overexpressed terms in IMU. Red: terms significant with FDR < 0.05 for both methylation and expression. C–F, Specific genes’ visualization from paradigmatic GO terms, top: DNA methylation profile across gene body with 30% gene length flank regions. Gray lines: IMU versus KRT significant DMRs. Orange lines: Significant cis-eQTMs overlapped with DMRs, middle: differential 5hmc peaks in IMU versus KRT, bottom: bar plot for subgroups’ log2cpm expression value with edgeR FDR values. Color: subgroups.

Funding

HHS | NIH | National Cancer Institute (NCI)

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ARTICLE ABSTRACT

This study revealed that the previously observed hypermethylation of HPV(+) HNSCC is due solely to the IMU subtype, illustrating the importance of fine-scale subtype analysis in such a heterogeneous disease. Particularly, IMU has significantly higher methylation of transposable elements, which can be tested as a prognosis biomarker in future translational studies.