Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

Cancer Genome Atlas Research Network, Grazi GL

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)194-212.e6
JournalCell Reports
Volume23
Issue number1
DOIs
Publication statusPublished - Apr 3 2018
Externally publishedYes

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Squamous Cell Carcinoma
Ports and harbors
Mutation
Genes
Atlases
Myeloid Cells
MicroRNAs
Oncogenes
Methylation
Chromatin
Smoking
Epithelial Cells
Inflammation
Gene Expression
Display devices
DNA
Therapeutics
Growth
Molecules

Cite this

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. / Cancer Genome Atlas Research Network; Grazi GL.

In: Cell Reports, Vol. 23, No. 1, 03.04.2018, p. 194-212.e6.

Research output: Contribution to journalArticle

Cancer Genome Atlas Research Network ; Grazi GL. / Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. In: Cell Reports. 2018 ; Vol. 23, No. 1. pp. 194-212.e6.
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