Comprehensive Genomic Characterization Of Head And Neck Squamous Cell Carcinomas
M. Lawrence, C. Sougnez, L. Lichtenstein, K. Cibulskis, E. Lander, S. Gabriel, G. Getz, A. Ally, M. Balasundaram, I. Birol, R. Bowlby, D. Brooks, Y. Butterfield, Rebecca Carlsen, D. Cheng, A. Chu, Noreen Dhalla, R. Guin, R. Holt, S. Jones, Darlene Lee, H. I. Li, M. Marra, Michael Mayo, R. Moore, A. Mungall, A. G. Robertson, J. Schein, Payal Sipahimalani, Angela Tam, N. Thiessen, T. Wong, A. Protopopov, Netty Santoso, Semin Lee, M. Parfenov, J. Zhang, Harshad S. Mahadeshwar, Jiabin Tang, Xiaojia Ren, Sahil Seth, Psalm S Haseley, D. Zeng, Lixing Yang, A. W. Xu, X. Song, Angeliki Pantazi, C. Bristow, Angela Hadjipanayis, J. Seidman, L. Chin, P. Park, R. Kucherlapati, Rehan Akbani, Tod D. Casasent, W. Liu, Y. Lu, G. B. Mills, Thomas C. Motter, J. Weinstein, L. Diao, J. Wang, Y. Fan, J. Liu, K. Wang, J. T. Auman, S. Balu, T. Bodenheimer, Elizabeth Buda, D. Hayes, K. Hoadley, Alan P. Hoyle, Stuart R. Jefferys, C. Jones, Patrick K. Kimes, Y. Liu, J. S. Marron, S. Meng, P. Mieczkowski, Lisle E. Mose, J. Parker, C. Perou, J. Prins, J. Roach, Y. Shi, Janae V. Simons, Darshan Singh, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, V. Walter, S. Waring, M. Wilkerson, J. Wu, N. Zhao, A. Cherniack, P. Hammerman, A. Tward, C. Pedamallu, G. Saksena, J. Jung, A. I. Ojesina, S. Carter, T. Zack, Steven E. Schumacher, Rameen Beroukhim, S. Freeman, M. Meyerson, J. Cho, Michael S. Noble, D. DiCara, H. Zhang, David I. Heiman, N. Gehlenborg, Doug Voet, P. Lin, S. Frazer, P. Stojanov, Y. Liu, L. Zou, J. Kim, D. M. Muzny, H. doddapaneni, Christie Kovar, Jeffrey S. Reid, Donna Morton, Y. Han, W. Hale, H. Chao, K. Chang, J. Drummond, R. Gibbs, Nipun Kakkar, D. Wheeler, L. Xi, Giovanni Ciriello, M. Ladanyi, W. Lee, Ricardo Ramírez, C. Sander, R. Shen, Rileen Sinha, N. Weinhold, B. Taylor, B. A. Aksoy, Gideon Dresdner, J. Gao, Benjamin E. Gross, Anders Jacobsen, B. Reva, N. Schultz, S. O. Sumer, Y. Sun, T. Chan, L. Morris, Joshua M. Stuart, S. Benz, Sam Ng, C. Benz, C. Yau, S. B. Baylin, L. Cope, L. Danilova, J. Herman, M. Bootwalla, D. Maglinte, P. Laird, T. Triche, D. Weisenberger, D. Berg, N. Agrawal, J. Bishop, P. Boutros, J. Bruce, L. Byers, J. Califano, T. Carey, Z. Chen, H. Cheng, S. Chiosea, E. E. Cohen, B. Diergaarde, A. Egloff, A. El-Naggar, R. Ferris, M. Frederick, J. Grandis, Y. Guo, R. Haddad, T. Harris, Angela B. Y. Hui, J. Lee, S. Lippman, Fei-fei Liu, J. Mchugh, J. Myers, P. Ng, B. Perez-Ordóñez, C. Pickering, M. B. Prystowsky, M. Romkes, A. Saleh, M. Sartor, R. Seethala, T. Seiwert, H. Si, C. V. Waes, Daryl Waggott, Maciej Wiznerowicz, W. Yarbrough, J. Zhang, Zhixiang Zuo, Ken Burnett, D. Crain, J. Gardner, Kevin W Lau, David Mallery, S. Morris, J. Paulauskis, R. Penny, C. Shelton, T. Shelton, M. Sherman, P. Yena, Aaron D. Black, Jay Bowen, J. Frick, J. Gastier‐Foster, H. Harper, Kristen M. Leraas, Tara M. Lichtenberg, N. Ramirez, L. Wise, E. Zmuda, J. Baboud, M. A. Jensen, Ari B. Kahn, Todd Pihl, D. Pot, Deepak Srinivasan, Jessica Walton, Yunhu Wan, Robert A. Burton, T. Davidsen, John A. Demchok, Greg Eley, M. L. Ferguson, K. Shaw, B. Ozenberger, Margi Sheth, H. Sofia, Roy Tarnuzzer, Zhi-Ning Wang, L. Yang, J. Zenklusen, C. Saller, Katherine Tarvin, C. Chen, R. Bollag, P. Weinberger, W. Golusiński, P. Golusiński, M. Ibbs, K. Korski, A. Mackiewicz, W. Suchorska, B. Szybiak, Erin Curley, Christina Beard, C. Mitchell, G. Sandusky, J. Ahn, Z. Khan, J. Irish, J. Waldron, W. William, Sophie C. Egea, C. Gómez-Fernández, Lynn M. Herbert, C. Bradford, D. Chepeha, A. Haddad, Tamara R. Jones, Christine M. Komarck, Mayya Malakh, J. S. Moyer, A. Nguyen, L. Peterson, M. E. Prince, L. Rozek, E. G. Taylor, H. Walline, G. T. Wolf, L. Boice, B. Chera, W. Funkhouser, M. Gulley, T. Hackman, M. Hayward, M. Huang, W. K. Rathmell, Ashley H. Salazar, W. Shockley, C. Shores, L. Thorne, Mark C. Weissler, Sylvia Wrenn, A. Zanation, B. Brown, M. Pham
Published 2015 · Medicine, Biology
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The Cancer Genome Atlas profiled 279 head and neck squamous cell carcinomas (HNSCCs) to provide a comprehensive landscape of somatic genomic alterations. Here we show that human-papillomavirus-associated tumours are dominated by helical domain mutations of the oncogene PIK3CA, novel alterations involving loss of TRAF3, and amplification of the cell cycle gene E2F1. Smoking-related HNSCCs demonstrate near universal loss-of-function TP53 mutations and CDKN2A inactivation with frequent copy number alterations including amplification of 3q26/28 and 11q13/22. A subgroup of oral cavity tumours with favourable clinical outcomes displayed infrequent copy number alterations in conjunction with activating mutations of HRAS or PIK3CA, coupled with inactivating mutations of CASP8, NOTCH1 and TP53. Other distinct subgroups contained loss-of-function alterations of the chromatin modifier NSD1, WNT pathway genes AJUBA and FAT1, and activation of oxidative stress factor NFE2L2, mainly in laryngeal tumours. Therapeutic candidate alterations were identified in most HNSCCs.
This paper references
Adults with Sotos syndrome: review of 21 adults with molecularly confirmed NSD1 alterations, including a detailed case report of the oldest person.
Matthew R Fickie (2011)
Comprehensive genomic characterization of squamous cell lung cancers
P. Hammerman (2012)
Critical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response
G. Oganesyan (2006)
Constitutive activation of distinct NF-κB signals in EBV-associated nasopharyngeal carcinoma.
Grace Tin-Yun Chung (2013)
Regulation of Hippo signaling by EGFR-MAPK signaling through Ajuba family proteins.
B. Reddy (2013)
Comprehensivemolecular characterization of clear cell renal cell carcinoma
C. Creighton (2013)
dbSNP: the NCBI database of genetic variation
S. Sherry (2001)
Constitutive activation of distinct NF-kappaB signals in EBV-associated nasopharyngeal carcinoma. The Journal of pathology
LIM Protein Ajuba Participates in the Repression of the ATR-Mediated DNA Damage Response
Sampada Kalan (2013)
Author manuscript; available in PMC 2015 July 29. Author Manuscript Author Manuscript Author Manuscript Author Manuscript
Human Papillomavirus (HPV) Upregulates the Cellular Deubiquitinase UCHL1 to Suppress the Keratinocyte's Innate Immune Response
Rezaul Karim (2013)
CD40-induced growth inhibition in epithelial cells is mimicked by Epstein-Barr Virus-encoded LMP1: involvement of TRAF3 as a common mediator.
A. Eliopoulos (1996)
Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma.
C. Annunziata (2007)
reconciling the dual roles of caspase 8 in cell death and survival
A. Oberst (2011)
Lack of MHC class I antigens and tumour aggressiveness of the squamous cell carcinoma of the larynx.
Francisco Javier Frutos Esteban (1990)
The Mutational Landscape of Head and Neck Squamous Cell Carcinoma
Nicolas Stransky (2011)
LIM protein Ajuba participates in the repression of the ATRmediated DNA damage response. Frontiers in genetics
S Kalan (2013)
Genetic Classification of Oral and Oropharyngeal Carcinomas Identifies Subgroups with a Different Prognosis
Serge J. Smeets (2009)
Molecular basis for CD40 signaling mediated by TRAF3.
C. Z. Ni (2000)
Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting
J. Sok (2006)
Ajuba is required for Rac activation and maintenance of E-cadherin adhesion
Sébastien Nola (2011)
An Epithelial–Mesenchymal Transition Gene Signature Predicts Resistance to EGFR and PI3K Inhibitors and Identifies Axl as a Therapeutic Target for Overcoming EGFR Inhibitor Resistance
L. Byers (2012)
Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras.
M. Mayo (1997)
Emerging landscape of oncogenic signatures across human cancers
Giovanni Ciriello (2013)
Integration sites of human papillomavirus 18 DNA sequences on HeLa cell chromosomes.
N. Popescu (1987)
competition for Raf kinase
NUP98–NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis
G. Wang (2007)
A transposon-based analysis of gene mutations related to skin cancer development.
Rita M Quintana (2013)
T.et al.dbSNP: the NCBIdatabaseofgenetic variation.NucleicAcidsRes
S. Sherry (2001)
Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression.
Peter J. Keating (1995)
Jeffrey V. Wong (2011)
Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.
Jacques Ferlay (2010)
Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes
Vonn Walter (2013)
Molecular basis for CD40 signaling mediated by TRAF3
HMGA2 is a driver of tumor metastasis.
A. Morishita (2013)
DeltaNp63 versatilely regulates a Broad NF-kappaB gene program and promotes squamous epithelial proliferation, migration, and inflammation. Cancer research
X Yang (2011)
Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1
N. Agrawal (2011)
Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF-kappaB and AP-1 activation and IL-8 and VEGF expression in human head and neck squamous cell carcinoma lines.
C. Bancroft (2002)
Transforming Fusions of FGFR and TACC Genes in Human Glioblastoma
Devendra Singh (2012)
LIM protein Ajuba participates in the repressionof theATR-mediatedDNAdamage
S. Kalan (2013)
The LIM protein Ajuba is required for ciliogenesis and left-right axis determination in medaka.
Yoko Nagai (2010)
Loss of transforming growth factor-beta type II receptor promotes metastatic head-and-neck squamous cell carcinoma.
Shi-Long Lu (2006)
Author manuscript; available in PMC
Acquisition of Host-Derived CD40L by HIV-1 In Vivo and Its Functional Consequences in the B-Cell Compartment † † Supplemental material for this article may be found at http://dx.doi.org/10.1128/JVI.01993-10.
Michaël Imbeault (2010)
Ajuba Family Proteins Link JNK to Hippo Signaling
Gongping Sun (2013)
Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3β-mediated phosphorylation of β-catenin
K. Haraguchi (2008)
The Catalogue of Somatic Mutations in Cancer (COSMIC).
S. Forbes (2008)
Human papillomavirus and survival of patients with oropharyngeal cancer.
K. Ang (2010)
Polo-like kinase 1 inhibitors, mitotic stress and the tumor suppressor p53
Mourad Sanhaji (2013)
Crosstalk of Notch with p53 and p63 in cancer growth control
Gian Paolo Dotto (2009)
Opposite role of Ras in tumor necrosis factor-alpha-induced cell cycle regulation: competition for Raf kinase.
Seung Jong Park (2001)
control of E2F dynamics in cell cycle entry
J. V. Wong (2011)
ΔNp63 versatilely regulates a Broad NF-κB gene program and promotes squamous epithelial proliferation, migration, and inflammation.
X. Yang (2011)
Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation
L. Morris (2013)
It cuts both ways: reconciling the dual roles of caspase 8 in cell death and survival
Andrew Oberst (2011)
COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA
The Cancer Genome Atlas Research Network (2013)
Molecular classification of head and neck squamous cell carcinomas using patterns of gene expression.
C. Chung (2004)
Somatic mutations lead to an oncogenic deletion of met in lung cancer.
Monica Kong-Beltran (2006)
Ajuba negatively regulates the Wnt signaling pathway by promoting GSK-3beta-mediated phosphorylation of beta-catenin.
K. Haraguchi (2008)
This paper is referenced by
Phase I trial of dacomitinib, a pan-human epidermal growth factor receptor (HER) inhibitor, with concurrent radiotherapy and cisplatin in patients with locoregionally advanced squamous cell carcinoma of the head and neck (XDC-001)
Amy Prawira (2016)
Human papillomaviruses: research priorities for the next decade.
Erika Langsfeld (2016)
SARS-CoV-2 infection induces EMT-like molecular changes, including ZEB1-mediated repression of the viral receptor ACE2, in lung cancer models
C. A. Stewart (2020)
Targeting Head and Neck Cancer Stem Cells
Andrew C. Birkeland (2015)
Similar Squamous Cell Carcinoma Epithelium microRNA Expression in Never Smokers and Ever Smokers
A. Kolokythas (2015)
Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy.
Andrew S. McDaniel (2015)
ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
Diego Beltran Alvarado (2017)
Comprehensive T-cell immunophenotyping and next-generation sequencing of human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinomas.
Kate Poropatich (2017)
Induction chemotherapy for head and neck cancer: is there still a role?
Roger Ove (2016)
Human papillomavirus oncoprotein E6 upregulates c-Met through p53 downregulation.
Guoqing Qian (2016)
Immune cells and prognosis in HPV-associated oropharyngeal squamous cell carcinomas: Review of the literature.
Camelia Nami Saber (2016)
Insertions and Deletions Target Lineage-Defining Genes in Human Cancers
Marcin Imielinski (2017)
Hepatocyte Growth Factor/c-Met Signaling in Head and Neck Cancer and Implications for Treatment
Natalie J. Rothenberger (2017)
Novel Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma
Darrin V Bann (2016)
Comprehensive Molecular Characterization of Salivary Duct Carcinoma Reveals Actionable Targets and Similarity to Apocrine Breast Cancer
Martin G Dalin (2016)
Targeted Therapy of Head and Neck Cancer
Damian T. Rieke (2016)
MicroRNA-Target Network Inference and Local Network Enrichment Analysis Identify Two microRNA Clusters with Distinct Functions in Head and Neck Squamous Cell Carcinoma
Steffen Sass (2015)
Repression of Wnt/β-catenin response elements by p63 (TP63)
Iyoko Katoh (2016)
Fibroblast growth factor family aberrations as a putative driver of head and neck squamous cell carcinoma in an epidemiologically low-risk patient as defined by targeted sequencing.
Brittny N. Tillman (2016)
Enhanced context reveals the scope of somatic missense mutations driving human cancers
Collin Tokheim (2018)
Analysis of head and neck carcinoma progression reveals novel and relevant stage-specific changes associated with immortalisation and malignancy
Ratna Veeramachaneni (2018)
HPV-Associated Oropharyngeal Cancer in the HIV/AIDS Patient.
Jennifer E. Cameron (2019)
Mechanism for oral tumor cell lysyl oxidase like-2 in cancer development: synergy with PDGF-AB
Faranak Mahjour (2019)
The failure of cetuximab-based de-intensified regimes for HPV-positive OPSCC: A radiobiologists perspective
Thorsten Rieckmann (2019)
Targeting the immune system in head and neck cancer.
Gilberto de Castro (2015)
Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival
Daniele Ramazzotti (2018)
The Tip of the Iceberg: Clinical Implications of Genomic Sequencing Projects in Head and Neck Cancer
Andrew C. Birkeland (2015)
A Review of HPV-Related Head and Neck Cancer
Kazuhiro Kobayashi (2018)
Human Papilloma Virus Increases ΔNp63α Expression in Head and Neck Squamous Cell Carcinoma
Simona Citro (2020)
Expression of the long noncoding RNA DINO in HPV positive cervical cancer cells reactivates the dormant TP53 tumor suppressor through ATM/CHK2 signaling
Surendra Sharma (2020)
Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition
Bernardo Rodriguez-Martin (2020)
Trimodality therapy for HPV-positive oropharyngeal cancer: A population-based study: Trimodality therapy for HPV+ OPC.
Nina N Sanford (2019)See more