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 - Liu, Yuexin
AU - Akbani, Rehan
AU - Byers, Lauren Averett
AU - Kanchi, Rupa S.
AU - Gay, Carl M.
AU - Diao, Lixia
AU - Ma, Wencai
AU - Lazar, Alexander J.
AU - Flores, Elsa R.
AU - Tsai, Kenneth Y.
AU - Zhang, Wei
AU - Broom, Bradley M.
AU - Ju, Zhenlin
AU - Korkut, Anil
AU - Li, Jun
AU - Liang, Han
AU - Ling, Shiyun
AU - Liu, Wenbin
AU - Lu, Yiling
AU - Mills, Gordon B.
AU - Rao, Arvind
AU - Weinstein, John N.
AU - Zhang, Jiexin
AU - Liu, Xiuping
AU - Wang, Linghua
AU - Fregnani, José H.
AU - Reis, Rui M.
AU - Ajani, Jaffer A.
AU - Behrens, Carmen
AU - Bondaruk, Jolanta
AU - Broaddus, Russell
AU - Czerniak, Bogdan
AU - Esmaeli, Bita
AU - Fujimoto, Junya
AU - Gershenwald, Jeffrey
AU - Guo, Charles
AU - Logothetis, Christopher
AU - Meric-Bernstam, Funda
AU - Moran, Cesar
AU - Ramondetta, Lois
AU - Rice, David
AU - Sood, Anil
AU - Tamboli, Pheroze
AU - Thompson, Timothy
AU - Troncoso, Patricia
AU - Tsao, Anne
AU - Wistuba, Ignacio
AU - Pickering, Curtis R.
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
UR - http://www.scopus.com/inward/citedby.url?scp=85044610513&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2018.03.063
DO - 10.1016/j.celrep.2018.03.063
M3 - Article
C2 - 29617660
AN - SCOPUS:85044610513
SN - 2211-1247
VL - 23
SP - 194-212.e6
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -