Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas.

Campbell, Joshua D; Yau, Christina; Bowlby, Reanne; Liu, Yuexin; Brennan, Kevin; Fan, Huihui; Taylor, Alison M; Wang, Chen; Walter, Vonn; Akbani, Rehan; Byers, Lauren Averett; Creighton, Chad J; Coarfa, Cristian; Shih, Juliann; Cherniack, Andrew D; Gevaert, Olivier; Prunello, Marcos; Shen, Hui; Anur, Pavana; Chen, Jianhong; ... (2018). Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas. Cell reports, 23(1), 194-212.e6. Cell Press 10.1016/j.celrep.2018.03.063

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Präzisionsonkologie

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2211-1247

Publisher:

Cell Press

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

01 Oct 2019 13:54

Last Modified:

24 Oct 2019 08:40

Publisher DOI:

10.1016/j.celrep.2018.03.063

PubMed ID:

29617660

Additional Information:

Mark Rubin (Direktor DBMR) ist Collaborator in dieser Publikation.

Uncontrolled Keywords:

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

BORIS DOI:

10.7892/boris.126387

URI:

https://boris.unibe.ch/id/eprint/126387

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