Journal article
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
Cell reports (Cambridge), Vol.23(1), pp.194-212.e6
04/03/2018
DOI: 10.1016/j.celrep.2018.03.063
PMCID: PMC6002769
PMID: 29617660
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 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.
Details
- Title: Subtitle
- Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
- Creators
- Joshua D Campbell - Massachusetts Institute of TechnologyChristina Yau - University of California, San FranciscoReanne Bowlby - BC Cancer AgencyYuexin Liu - The University of Texas MD Anderson Cancer CenterKevin Brennan - Stanford UniversityHuihui Fan - Van Andel InstituteAlison M Taylor - Massachusetts Institute of TechnologyChen Wang - Mayo ClinicVonn Walter - Penn State Milton S. Hershey Medical CenterRehan Akbani - The University of Texas MD Anderson Cancer CenterLauren Averett Byers - The University of Texas MD Anderson Cancer CenterChad J Creighton - Baylor College of MedicineCristian Coarfa - Baylor College of MedicineJuliann Shih - Massachusetts Institute of TechnologyAndrew D Cherniack - Massachusetts Institute of TechnologyOlivier Gevaert - Stanford UniversityMarcos Prunello - Stanford UniversityHui Shen - Van Andel InstitutePavana Anur - Oregon Health & Science UniversityJianhong Chen - National Institutes of HealthHui Cheng - National Institutes of HealthD Neil Hayes - University of North Carolina at Chapel HillSusan Bullman - Massachusetts Institute of TechnologyChandra Sekhar Pedamallu - Massachusetts Institute of TechnologyAkinyemi I Ojesina - University of Alabama at BirminghamSara Sadeghi - BC Cancer AgencyKaren L Mungall - BC Cancer AgencyA Gordon Robertson - BC Cancer AgencyChristopher Benz - Buck Institute for Research on AgingAndre Schultz - The University of Texas MD Anderson Cancer CenterRupa S Kanchi - The University of Texas MD Anderson Cancer CenterCarl M Gay - The University of Texas MD Anderson Cancer CenterApurva Hegde - The University of Texas MD Anderson Cancer CenterLixia Diao - The University of Texas MD Anderson Cancer CenterJing Wang - The University of Texas MD Anderson Cancer CenterWencai Ma - The University of Texas MD Anderson Cancer CenterPavel Sumazin - Baylor College of MedicineHua-Sheng Chiu - Baylor College of MedicineTing-Wen Chen - Baylor College of MedicinePreethi Gunaratne - University of HoustonLarry Donehower - Baylor College of MedicineJanet S Rader - Medical College of WisconsinRosemary Zuna - University of Oklahoma Health Sciences CenterHikmat Al-Ahmadie - Memorial Sloan Kettering Cancer CenterAlexander J Lazar - The University of Texas MD Anderson Cancer CenterElsa R Flores - Moffitt Cancer CenterKenneth Y Tsai - Moffitt Cancer CenterJane H Zhou - Roswell Park Cancer InstituteAnil K Rustgi - University of PennsylvaniaEsther Drill - Memorial Sloan Kettering Cancer CenterRonglei Shen - Memorial Sloan Kettering Cancer CenterChristopher K Wong - University of California, Santa CruzJoshua M Stuart - University of California, Santa CruzPeter W Laird - Van Andel InstituteKatherine A Hoadley - University of North Carolina at Chapel HillJohn N Weinstein - The University of Texas MD Anderson Cancer CenterMyron Peto - Oregon Health & Science UniversityCurtis R Pickering - The University of Texas MD Anderson Cancer CenterZhong Chen - National Institutes of HealthCarter Van Waes - National Institutes of HealthCancer Genome Atlas Research Network
- Contributors
- Mohammed M Milhem (Contributor) - University of Iowa, Hematology, Oncology, and Blood & Marrow Transplantation
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.23(1), pp.194-212.e6
- DOI
- 10.1016/j.celrep.2018.03.063
- PMID
- 29617660
- PMCID
- PMC6002769
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Grant note
- U24 CA143843 / NCI NIH HHS U24 CA199461 / NCI NIH HHS U24 CA210957 / NCI NIH HHS P30 CA225520 / NCI NIH HHS ZIA DC000016-24 / Intramural NIH HHS U54 HG003079 / NHGRI NIH HHS P30 CA016672 / NCI NIH HHS P30 ES010126 / NIEHS NIH HHS U24 CA143883 / NCI NIH HHS U24 CA210990 / NCI NIH HHS U24 CA210969 / NCI NIH HHS U24 CA143799 / NCI NIH HHS R01 CA194062 / NCI NIH HHS U24 CA210988 / NCI NIH HHS ZIA DC000074-09 / Intramural NIH HHS U24 CA143867 / NCI NIH HHS U24 CA143858 / NCI NIH HHS U24 CA143882 / NCI NIH HHS P30 CA008748 / NCI NIH HHS ZID DC000075-09 / Intramural NIH HHS U54 HG003067 / NHGRI NIH HHS U24 CA143845 / NCI NIH HHS U24 CA143835 / NCI NIH HHS U54 HG003273 / NHGRI NIH HHS U24 CA143840 / NCI NIH HHS U24 CA144025 / NCI NIH HHS R35 CA197452 / NCI NIH HHS U24 CA143866 / NCI NIH HHS U24 CA210950 / NCI NIH HHS P01 CA098101 / NCI NIH HHS U24 CA210949 / NCI NIH HHS U24 CA143848 / NCI NIH HHS R01 CA163722 / NCI NIH HHS T32 CA009666 / NCI NIH HHS
- Language
- English
- Date published
- 04/03/2018
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984360041902771
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