Comprehensive genomic characterization of head and neck squamous cell carcinomas

  title={Comprehensive genomic characterization of head and neck squamous cell carcinomas},
  author={Michael S. Lawrence and Carrie Sougnez and Lee T Lichtenstein and Kristian Cibulskis and Eric S. Lander and S. Gabriel and Gad Getz and Adrian Ally and Miruna Balasundaram and Inanç Birol and Reanne Bowlby and Denise Brooks and Yaron S. N. Butterfield and Rebecca Carlsen and Dean Cheng and Andy Chu and Noreen Dhalla and Ranabir Guin and Robert A. Holt and Steven J. M. Jones and Darlene Lee and Haiyan Irene Li and Marco A. Marra and Michael Mayo and Richard A. Moore and Andrew J. Mungall and A. Gordon Robertson and Jacqueline E. Schein and Payal Sipahimalani and Angela Tam and Nina Thiessen and Tina Wong and Alexei Protopopov and Netty G Santoso and Semin Lee and Michael G Parfenov and Jianhua Zhang and Harshad S. Mahadeshwar and Jiabin Tang and Xiaojia Ren and Sahil Seth and Psalm S Haseley and Dong Zeng and Lixing Yang and Andrew Wei Xu and Xingzhi Song and Angeliki Pantazi and Christopher Aaron Bristow and Angela Hadjipanayis and Jonathan G. Seidman and Lynda Chin and Peter J. Park and Raju Kucherlapati and Rehan Akbani and Tod D. Casasent and Wenbin Liu and Yiling Lu and Gordon B. Mills and Thomas C. Motter and John N. Weinstein and Lixia Diao and Jing Wang and Youhong Fan and Jinze Liu and Kai Wang and James T. Auman and Saianand Balu and Tom Bodenheimer and Elizabeth Buda and David Neil Hayes and Katherine A. Hoadley and Alan Hoyle and Stuart R. Jefferys and Corbin D. Jones and Patrick K. Kimes and Yufeng Liu and J. S. Marron and Shaowu Meng and Piotr A. Mieczkowski and Lisle E. Mose and Joel S. Parker and Charles M. Perou and Jan Prins and Jeffrey M. Roach and Yan Shi and Janae V. Simons and Darshan Singh and Matthew G. Soloway and Donghui Tan and Umadevi Veluvolu and Vonn Walter and Scot Michael Waring and Matthew D. Wilkerson and Junyuan Wu and Ni Zhao and Andrew D. Cherniack and Peter S. Hammerman and Aaron D. Tward and Chandra Sekhar Pedamallu and Gordon Saksena and Joonil Jung and Akinyemi I. Ojesina and Scott L. Carter and T. Zack and Steven E Schumacher and Rameen Beroukhim and Samuel S. Freeman and Matthew L Meyerson and Juok Cho and Michael S. Noble and Danielle M. Dicara and Hailei Zhang and David I. Heiman and Nils Gehlenborg and Douglas Voet and Pei Lin and Scott R. Frazer and Petar Stojanov and YingChun Liu and Lihua Zou and Jaegil Kim and Donna M. Muzny and Harshavardhan Doddapaneni and Christie L. Kovar and Jeffrey S. Reid and Donna Morton and Yi Han and Walker Hale and Hsu Chao and Kyle Chang and Jennifer Drummond and Richard A. Gibbs and Nipun Kakkar and David A. Wheeler and Liu Xi and Giovanni Domenico Ciriello and Marc Ladanyi and William Lee and Ricardo Ramirez and Chris Sander and Ronglai Shen and Rileen Sinha and Nils Weinhold and Barry S. Taylor and B{\"u}lent Arman Aksoy and Gideon Dresdner and Jianjiong Gao and Benjamin E. Gross and Anders S. Jacobsen and Boris Reva and Nikolaus D. Schultz and Selcuk Onur Sumer and Yichao Sun and Timothy A. Chan and Luc G. T. Morris and Joshua M. Stuart and Stephen Charles Benz and Sam Ng and Christopher C. Benz and Christina Yau and Stephen B. Baylin and Leslie M. Cope and Ludmila V. Danilova and James Gordon Herman and Moiz S. Bootwalla and Dennis T. Maglinte and Peter W. Laird and Timothy J. Triche and Daniel J. Weisenberger and David J. Van Den Berg and Nishant Agrawal and Justin A. Bishop and Paul C. Boutros and Jeff Bruce and Lauren Averett Byers and Joseph A. Califano and Thomas E. Carey and Zhong Chen and Hui Cheng and Simion I. Chiosea and Ezra E. W. Cohen and Brenda Diergaarde and Ann Marie Egloff and Adel K El-Naggar and Robert L Ferris and Mitchell J Frederick and Jennifer R. Grandis and Yanzhu Guo and Robert I Haddad and Thomas M. Harris and Angela Bik-Yu Hui and Jiun-Kae Jack Lee and Scott M. Lippman and Fei-Fei Liu and Jonathan B Mchugh and Jeffrey N. Myers and Patrick Kwok Shing Ng and B. Perez-Ordonez and Curtis R. Pickering and Michael B. Prystowsky and Marjorie Romkes and Anthony D. Saleh and Maureen A. Sartor and Raja R. Seethala and Tanguy Y. Seiwert and Haishan Si and Carter van Waes and Daryl Waggott and Maciej Wiznerowicz and Wendell Gray Yarbrough and Jiexin Zhang and Zhixiang Zuo and K. Burnett and Daniel Crain and Johanna Gardner and Kevin R Lau and David W Mallery and Scott Morris and Joseph D. Paulauskis and Robert J. Penny and Candace Shelton and Troy Shelton and Mark E. Sherman and Peggy Yena and Aaron D. Black and Jay Bowen and Jessica Frick and Julie M. Gastier-Foster and Hollie A. Harper and Kristen Leraas and Tara M. Lichtenberg and Nilsa C. Ramirez and Lisa Wise and E J Zmuda and Julien Baboud and Mark A. Jensen and Ari B. Kahn and Todd Pihl and David Pot and Deepak Srinivasan and Jessica L Walton and Yunhu Wan and Robert A. Burton and Tanja Davidsen and John A. Demchok and Greg Eley and Martin L Ferguson and Kenna R. Mills Shaw and Bradley A Ozenberger and Margi Sheth and Heidi J. Sofia and Roy W. Tarnuzzer and Zhining Wang and Liming Yang and Jean Claude Zenklusen and Charles Saller and Katherine Tarvin and Chu Chen and Roni J. Bollag and Paul Maurice Weinberger and Wojciech Golusiński and Paweł Golusiński and Matthew Ibbs and Konstanty Korski and Andrzej Adam Mackiewicz and Wiktoria Maria Suchorska and Bartosz Szybiak and Erin E. Curley and Christina Joye Beard and Colleen M. Mitchell and George E Sandusky and Julie Ahn and Zubair Khan and Jonathan C. Irish and John N. Waldron and William N. William and Sophie C. Egea and Carmen R. Gomez-Fernandez and Lynn M. Herbert and Carol Rossier Bradford and Douglas B. Chepeha and Andrea Haddad and Tamara R. Jones and Christine M. Komarck and Mayya Malakh and Jeffrey S Moyer and Ariane Nguyen and Lisa A. Peterson and Mark E P Prince and Laura S. Rozek and Evan G. Taylor and Heather M Walline and Gregory T Wolf and L. Peter Boice and Bhishamjit S. Chera and William K. Funkhouser and Margaret L. Gulley and Trevor G. Hackman and Michele C Hayward and Meijuan Huang and W. Rathmell and Ashley H. Salazar and William W Shockley and Carol G. Shores and Leigh B. Thorne and Mark Christian Weissler and Sylvia Wrenn and Adam Mikial Zanation and Brandee T. Brown and Michelle Pham},
  pages={576 - 582}
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… 

Molecular genetics of head and neck squamous cell carcinoma

Despite the increasingly precise genomic characterization of HNSCCs, precision medicine is struggling to find its place in the management of H NSCCs.

Comprehensive Genomic Review of TCGA Head and Neck Squamous Cell Carcinomas (HNSCC)

Survition analysis revealed that overexpression of some oncogenes, such as EGFR, CDK6 or CDK4 were associated with poorer prognosis tumours, and functional analysis determined that tissue development and cell differentiation were the most relevant signalling pathways in upregulated and downregulated genes.

Comprehensive Genomic Review of TCGA Head and Neck Squamous Cell Carcinomas (HNSCC).

Survival analysis revealed that overexpression of some oncogenes, such as EGFR, CDK6 or CDK4 were associated with poorer prognosis tumours, and these new findings help to develop new therapies and programs for the prevention of HNSCC.

TP53 mutations in head and neck cancer

Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC.

Analysis of head and neck carcinoma progression reveals novel and relevant stage-specific changes associated with immortalisation and malignancy

Changes in the genomic landscape in the development of HNSCC from potentially premalignant lesions (PPOLS) to malignancy and lymph node metastases are reported, supporting a role for CSMD1 inactivation in early head and neck carcinogenesis and identifying mutations in genes and an increase or decrease in number of copies of genes.

Molecular progression of head and neck squamous cell carcinoma

  • Santu Kumar SahaGuru Prasad MaitiSusanta RoychoudhuryC. Panda
  • Biology, Medicine
    The Nucleus
  • 2017
Systemic approach has been taken to characterize the molecular pathways in this tumor to find out the key regulatory steps for management of the disease.

Mutational landscape of head and neck squamous cell carcinomas in a South Asian population

The results of this study can guide a better mechanistic understanding of HNSCC in the population, ultimately contributing new, rational therapeutic targets for the treatment of the disease.

TP53 Mutations in Head and Neck Squamous Cell Carcinoma and Their Impact on Disease Progression and Treatment Response

Clinically, TP53 mutations are significantly associated with short survival time and tumor resistance to radiotherapy and chemotherapy in HNSCC patients, which makes the TP53 mutation status a potentially useful molecular factor for risk stratification and predictor of clinical response in these patients.

The Landscape of Somatic Copy Number Alterations in Head and Neck Squamous Cell Carcinoma

A meta-analysis of CNAs for HNSCC samples revealed a sub-cluster predominantly composed of nasopharynx tumors and presented a large proportion of HPV-positive samples, which will facilitate the discovery of therapeutic candidates and extend the molecular understanding of H NSCC.



The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

The results indicate the ability of large-scale sequencing to reveal fundamental tumorigenic mechanisms and suggest the development of targeted therapies for head and neck cancer may be hindered by complex mutational profiles.

Molecular Subtypes in Head and Neck Cancer Exhibit Distinct Patterns of Chromosomal Gain and Loss of Canonical Cancer Genes

Four molecular classes of HNSCC are confirmed consistent with signatures established for squamous carcinoma of the lung, including deregulation of the KEAP1/NFE2L2 oxidative stress pathway, differential utilization of the lineage markers SOX2 and TP63, and preference for the oncogenes PIK3CA and EGFR.

Comprehensive genomic characterization of squamous cell lung cancers

It is shown that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour.

Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1

To explore the genetic origins of head and neck squamous cell carcinoma, whole-exome sequencing and gene copy number analyses were used to study 32 primary tumors and identified mutations in FBXW7 and NotCH1, suggesting that NOTCH1 may function as a tumor suppressor gene rather than an oncogene in this tumor type.


Remodelling cellular metabolism constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.

Comprehensivemolecular characterization of clear cell renal cell carcinoma

Remodelling cellular metabolism constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.

Loss of transforming growth factor-beta type II receptor promotes metastatic head-and-neck squamous cell carcinoma.

It is reported that overexpression of K-ras or H-ras and loss of transforming growth factor-beta type II receptor (TGFbetaRII) are common events in human HNSCC and that targeting common oncogenic pathways in tumor epithelia together with blocking the effect of TGFbeta1 on tumor stroma may provide a novel therapeutic strategy for H NSCC.

Genetic Classification of Oral and Oropharyngeal Carcinomas Identifies Subgroups with a Different Prognosis

In conclusion, the discovery of these new classes of oral and oropharyngeal cancer with unique genetic and clinical characteristics has important consequences for future basic and clinical studies.

Recurrent somatic mutation of FAT1 in multiple human cancers leads to aberrant Wnt activation

Recurrent somatic mutations of the Drosophila melanogaster tumor suppressor–related gene FAT1 in glioblastoma, colorectal cancer, and head and neck cancer strongly point to FAT1 as a tumor suppressing gene driving loss of chromosome 4q35, a prevalent region of deletion in cancer.