Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

The Cancer Genome Atlas Research Network

Research output: Contribution to journalArticle

50 Scopus citations

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. Campbell et al. reveal that squamous cell cancers from different tissue sites may be distinguished from other cancers and subclassified molecularly by recurrent alterations in chromosomes, DNA methylation, messenger and microRNA expression, or by mutations. These affect squamous cell pathways and programs that provide candidates for therapy.

Original languageEnglish (US)
Pages (from-to)194-212.e6
JournalCell Reports
Volume23
Issue number1
DOIs
StatePublished - Apr 3 2018

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Keywords

  • bladder carcinoma with squamous differentiation
  • cervical squamous cell carcinoma
  • esophageal squamous cell carcinoma
  • genomics
  • head and neck squamous cell carcinoma
  • human papillomavirus
  • lung squamous cell carcinoma
  • proteomics
  • transcriptomics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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