Genomic, pathway network, and immunologic features distinguishing squamous carcinomas Journal Article


Authors: Campbell, J. D.; Yau, C.; Bowlby, R.; Liu, Y.; Brennan, K.; Fan, H.; Taylor, A. M.; Wang, C.; Walter, V.; Akbani, R.; Byers, L. A.; Creighton, C. J.; Coarfa, C.; Shih, J.; Cherniack, A. D.; Gevaert, O.; Prunello, M.; Shen, H.; Anur, P.; Chen, J.; Cheng, H.; Hayes, D. N.; Bullman, S.; Pedamallu, C. S.; Ojesina, A. I.; Sadeghi, S.; Mungall, K. L.; Robertson, A. G.; Benz, C.; Schultz, A.; Kanchi, R. S.; Gay, C. M.; Hegde, A.; Diao, L.; Wang, J.; Ma, W.; Sumazin, P.; Chiu, H. S.; Chen, T. W.; Gunaratne, P.; Donehower, L.; Rader, J. S.; Zuna, R.; Al-Ahmadie, H.; Lazar, A. J.; Flores, E. R.; Tsai, K. Y.; Zhou, J. H.; Rustgi, A. K.; Drill, E.; Shen, R.; Wong, C. K.; The Cancer Genome Atlas Research Network; Stuart, J. M.; Laird, P. W.; Hoadley, K. A.; Weinstein, J. N.; Pickering, C. R.; Zhang, J.; Chen, Z.; Van Waes, C.
Article Title: Genomic, pathway network, and immunologic features distinguishing squamous carcinomas
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. © 2018
Keywords: signal transduction; adolescent; adult; child; human tissue; protein expression; aged; unclassified drug; gene mutation; human cell; major clinical study; promoter region; squamous cell carcinoma; nonhuman; cell death; dna damage; gene; cancer susceptibility; microrna; gene expression; cell growth; inflammation; cohort analysis; smoking; cell differentiation; mutational analysis; proteomics; transcriptomics; dna methylation; immunoregulation; regulatory t lymphocyte; immunotherapy; messenger rna; chromatin; cpg island; gene repression; mitogen activated protein kinase 1; genomics; ras protein; caspase 8; oxidative stress; dna mutational analysis; lung squamous cell carcinoma; gene dosage; genetic predisposition; chromosome 11q; esophageal squamous cell carcinoma; chromosome 14q; chromosome 3q; wart virus; miosis; head and neck squamous cell carcinoma; tumor immunology; human papillomavirus; epithelial mesenchymal transition; chromosome 5q; fanconi anemia group f protein; human; male; female; priority journal; article; myeloid-derived suppressor cell; tet1 gene; bladder carcinoma with squamous differentiation; cervical squamous cell carcinoma; microrna 944; fancf gene
Journal Title: Cell Reports
Volume: 23
Issue: 1
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2018-04-03
Start Page: 194
End Page: 212.e6
Language: English
DOI: 10.1016/j.celrep.2018.03.063
PROVIDER: scopus
PUBMED: 29617660
PMCID: PMC6002769
DOI/URL:
Notes: Ronglai Shen's first name is misspelled on the original publication -- Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Ronglai Shen
    192 Shen
  2. Esther Naomi Drill
    72 Drill