Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas


Joshua D. Campbell, Dana-Farber Cancer Institute
Christina Yau, University of California, San Francisco
Reanne Bowlby, British Columbia Cancer Agency
Yuexin Liu, University of Texas MD Anderson Cancer Center
Kevin Brennan, Stanford University
Huihui Fan, Van Andel Research Institute
Alison M. Taylor, Dana-Farber Cancer Institute
Chen Wang, Mayo Clinic
Vonn Walter, Penn State Health Milton S. Hershey Medical Center
Rehan Akbani, University of Texas MD Anderson Cancer Center
Lauren Averett Byers, University of Texas MD Anderson Cancer Center
Chad J. Creighton, University of Texas MD Anderson Cancer Center
Cristian Coarfa, Baylor College of Medicine
Juliann Shih, Dana-Farber Cancer Institute
Andrew D. Cherniack, Dana-Farber Cancer Institute
Olivier Gevaert, Stanford University
Marcos Prunello, Stanford University
Hui Shen, Van Andel Research Institute
Pavana Anur, Oregon Health & Science University
Jianhong Chen, National Institute on Deafness and Other Communication Disorders (NIDCD)
Hui Cheng, National Institute on Deafness and Other Communication Disorders (NIDCD)
D. Neil Hayes, The University of North Carolina at Chapel Hill
Susan Bullman, Dana-Farber Cancer Institute
Chandra Sekhar Pedamallu, Dana-Farber Cancer Institute
Akinyemi I. Ojesina, The University of Alabama at Birmingham
Sara Sadeghi, British Columbia Cancer Agency
Karen L. Mungall, British Columbia Cancer Agency
A. Gordon Robertson, British Columbia Cancer Agency
Christopher Benz, Buck Institute for Age Research
Andre Schultz, University of Texas MD Anderson Cancer Center
Rupa S. Kanchi, University of Texas MD Anderson Cancer Center
Carl M. Gay, University of Texas MD Anderson Cancer Center
Apurva Hegde, University of Texas MD Anderson Cancer Center

Document Type

Journal Article

Publication Date



Cell Reports








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


© 2018 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.

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