23
IRUS Total
Downloads
  Altmetric

Genomic, pathway network, and immunologic features distinguishing squamous carcinomas

File Description SizeFormat 
1-s2.0-S2211124718304248-main.pdfPublished version7.9 MBAdobe PDFView/Open
Title: Genomic, pathway network, and immunologic features distinguishing squamous carcinomas
Authors: Campbell, JD
Yau, C
Bowlby, R
Liu, Y
Brennan, K
Fan, H
Taylor, AM
Wang, C
Walter, V
Akbani, R
Byers, LA
Creighton, CJ
Coarfa, C
Shih, J
Cherniack, AD
Gevaert, O
Prunello, M
Shen, H
Anur, P
Chen, J
Cheng, H
Hayes, DN
Bullman, S
Pedamallu, CS
Ojesina, AI
Sadeghi, S
Mungall, KL
Robertson, AG
Benz, C
Schultz, A
Kanchi, RS
Gay, CM
Hegde, A
Diao, L
Wang, J
Ma, W
Sumazin, P
Chiu, H-S
Chen, T-W
Gunaratne, P
Donehower, L
Rader, JS
Zuna, R
Al-Ahmadie, H
Lazar, AJ
Flores, ER
Tsai, KY
Zhou, JH
Rustgi, AK
Drill, E
Shen, R
Wong, CK
Stuart, JM
Laird, PW
Hoadley, KA
Weinstein, JN
Peto, M
Pickering, CR
Chen, Z
Van Waes, C
Item 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.
Issue Date: 3-Apr-2018
Date of Acceptance: 15-Mar-2018
URI: http://hdl.handle.net/10044/1/71264
DOI: https://doi.org/10.1016/j.celrep.2018.03.063
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/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
CELL CARCINOMA
FANCONI-ANEMIA
ANTITUMOR-ACTIVITY
HUMAN HEAD
INHIBITOR
EXPRESSION
PHOSPHORYLATION
PROTEINS
CANCERS
GENES
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
Cancer Genome Atlas Research Network
Science & Technology
Life Sciences & Biomedicine
Cell Biology
CELL CARCINOMA
FANCONI-ANEMIA
ANTITUMOR-ACTIVITY
HUMAN HEAD
INHIBITOR
EXPRESSION
PHOSPHORYLATION
PROTEINS
CANCERS
GENES
Publication Status: Published
Open Access location: http://www.cell.com/cell-reports/retrieve/pii/S2211124718304248?_returnURL=https:%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2211124718304248%3Fshowall%3Dtrue
Online Publication Date: 2018-04-05
Appears in Collections:Department of Surgery and Cancer