1. Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
- Author
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Rustgi, A.K., Cherniack, A.D., Weinstein, J.N., Stuart, J.M., Bowlby, R., Diao, L., Gevaert, O., Schultz, A., The Cancer Genome Atlas Research Network, Taylor, A.M., Walter, V., Lazar, A.J., Chen, J., Flores, E.R., Hoadley, K.A., Laird, P.W., Sadeghi, S., Yau, C., Drill, E., Cheng, H., Anur, P., Mungall, K.L., Tsai, K.Y., Zuna, R., Gunaratne, P., Donehower, L., Chen, Z., Gay, C.M., Pickering, C.R., Van Waes, C., Coarfa, C., Wang, C., Peto, M., Ojesina, A.I., Hegde, A., Shen, R., Pedamallu, C.S., Liu, Y., Shih, J., Wong, C.K., Prunello, M., Kanchi, R.S., Wang, J., Al-Ahmadie, H., Chiu, H.-S., Zhou, J.H., Akbani, R., Brennan, K., Shen, H., Ma, W., Benz, C., Sumazin, P., Fan, H., Hayes, D.N., Byers, L.A., Bullman, S., Campbell, J.D., Rader, J.S., Robertson, A.G., Creighton, C.J., and Chen, T.-W.
- Subjects
Epithelial-Mesenchymal Transition ,Medical Physiology ,Cancer Genome Atlas Research Network ,head and neck squamous cell carcinoma ,Cell Line ,transcriptomics ,proteomics ,Genetic ,genomics ,lung squamous cell carcinoma ,Genetics ,Humans ,2.1 Biological and endogenous factors ,Polymorphism ,Aetiology ,human papillomavirus ,Cancer ,Neoplastic ,Tumor ,Carcinoma ,Human Genome ,bladder carcinoma with squamous differentiation ,DNA Methylation ,esophageal squamous cell carcinoma ,stomatognathic diseases ,Squamous Cell ,Gene Expression Regulation ,cervical squamous cell carcinoma ,Sexually Transmitted Infections ,Biochemistry and Cell Biology ,Metabolic Networks and Pathways ,Biotechnology - 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 ��Np63 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.
- Published
- 2018