TY - JOUR
T1 - Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
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 - Sumazin, Pavel
AU - Chiu, Hua Sheng
AU - Chen, Ting Wen
AU - Gunaratne, Preethi
AU - Donehower, Larry
AU - Rader, Janet S.
AU - Zuna, Rosemary
AU - Al-Ahmadie, Hikmat
AU - Lazar, Alexander J.
AU - Flores, Elsa R.
AU - Tsai, Kenneth Y.
AU - Zhou, Jane H.
AU - Rustgi, Anil K.
AU - Drill, Esther
N1 - Publisher Copyright:
© 2018
PY - 2018/4/3
Y1 - 2018/4/3
N2 - 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.
AB - 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.
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
UR - http://www.scopus.com/inward/record.url?scp=85044610513&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.03.063
DO - 10.1016/j.celrep.2018.03.063
M3 - 文章
C2 - 29617660
AN - SCOPUS:85044610513
SN - 2211-1247
VL - 23
SP - 194-212.e6
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -