27 Citations (Scopus)

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

Fingerprint

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

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)

Cite this

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

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

Research output: Contribution to journalArticle

The Cancer Genome Atlas Research Network. / 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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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.",
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AU - The Cancer Genome Atlas Research Network

AU - Campbell, Joshua D.

AU - Yau, Christina

AU - Bowlby, Reanne

AU - Liu, Yuexin

AU - Brennan, Kevin

AU - Fan, Huihui

AU - Taylor, Alison M.

AU - Wang, Chen

AU - Walter, Vonn

AU - Akbani, Rehan

AU - Byers, Lauren Averett

AU - Creighton, Chad J.

AU - Coarfa, Cristian

AU - Shih, Juliann

AU - Cherniack, Andrew D.

AU - Gevaert, Olivier

AU - Prunello, Marcos

AU - Shen, Hui

AU - Anur, Pavana

AU - Chen, Jianhong

AU - Cheng, Hui

AU - Hayes, D. Neil

AU - Bullman, Susan

AU - Pedamallu, Chandra Sekhar

AU - Ojesina, Akinyemi I.

AU - Sadeghi, Sara

AU - Mungall, Karen L.

AU - Robertson, A. Gordon

AU - Benz, Christopher

AU - Schultz, Andre

AU - Kanchi, Rupa S.

AU - Gay, Carl M.

AU - Hegde, Apurva

AU - Diao, Lixia

AU - Wang, Jing

AU - Ma, Wencai

AU - Borad, Mitesh J

AU - Chandan, Vishal

AU - Cheville, John

AU - Copland, John A III

AU - Flotte, Thomas J

AU - Kendrick, Michael

AU - Kocher, Jean-Pierre

AU - O'Neill, Brian Patrick

AU - Patel, Tushar C

AU - Petersen, Gloria M

AU - Roberts, Lewis Rowland

AU - Smallridge, Robert Christian

AU - Stanton, Melissa

AU - Zhang, Lizhi

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KW - bladder carcinoma with squamous differentiation

KW - cervical squamous cell carcinoma

KW - esophageal squamous cell carcinoma

KW - genomics

KW - head and neck squamous cell carcinoma

KW - human papillomavirus

KW - lung squamous cell carcinoma

KW - proteomics

KW - transcriptomics

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