Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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Publications → Summary Page: PanCanAtlas Publications → Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
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PanCanAtlas
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Cancer Reports. Volume 23, Issue 1 p194-212.e6, 3 April 2018 10.1016/j.celrep.2018.03.063

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, that are correlated with 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 DNp63 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 new possibilities for molecular classification and therapeutic approaches.

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