Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation. Low-CNA SCCs tended to be HPV(+) and display hypermethylation with repression of TET1 demethylase and FANCF, previously linked to predisposition to SCC, or harbor mutations affecting CASP8, RAS-MAPK pathways, chromatin modifiers, and immunoregulatory molecules. We uncovered hypomethylation of the alternative promoter that drives expression of the ΔNp63 oncogene and embedded miR944. Co-expression of immune checkpoint, T-regulatory, and Myeloid suppressor cells signatures may explain reduced efficacy of immune therapy. These findings support possibilities for molecular classification and therapeutic approaches.
Duke Scholars
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Related Subject Headings
- Polymorphism, Genetic
- Metabolic Networks and Pathways
- Humans
- Genomics
- Gene Expression Regulation, Neoplastic
- Epithelial-Mesenchymal Transition
- DNA Methylation
- Cell Line, Tumor
- Carcinoma, Squamous Cell
- 31 Biological sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Polymorphism, Genetic
- Metabolic Networks and Pathways
- Humans
- Genomics
- Gene Expression Regulation, Neoplastic
- Epithelial-Mesenchymal Transition
- DNA Methylation
- Cell Line, Tumor
- Carcinoma, Squamous Cell
- 31 Biological sciences