| 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 |
| Contributors: |
SAIC-F-Frederick, Inc; Leidos Biomedical Research, Inc. |
| Source: |
212 ; 194 |
| Publisher Information: |
Elsevier |
| Publication Year: |
2018 |
| Collection: |
Imperial College London: Spiral |
| Subject Terms: |
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 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Cell Reports; http://hdl.handle.net/10044/1/71264; https://doi.org/10.1016/j.celrep.2018.03.063; TCGA Pilot Program; 15Y011ST |
| DOI: |
10.1016/j.celrep.2018.03.063 |
| Availability: |
http://hdl.handle.net/10044/1/71264; https://doi.org/10.1016/j.celrep.2018.03.063 |
| Rights: |
© 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/). |
| Accession Number: |
edsbas.41BF4AF2 |
| Database: |
BASE |