Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2018-04-03
Date Acceptance
2018-03-15
Citation
Cell Reports, 2018, 23 (1), pp.194-212
ISSN
2211-1247
Publisher
Elsevier
Start Page
194
End Page
212
Journal / Book Title
Cell Reports
Volume
23
Issue
1
Copyright Statement
© 2018 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor
SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000429092900018&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
TCGA Pilot Program
15Y011ST
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
CELL CARCINOMA
FANCONI-ANEMIA
ANTITUMOR-ACTIVITY
HUMAN HEAD
INHIBITOR
EXPRESSION
PHOSPHORYLATION
PROTEINS
CANCERS
GENES
Publication Status
Published
Date Publish Online
2018-04-05