Title |
Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors
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Published in |
Genome Medicine, May 2013
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DOI | 10.1186/gm453 |
Pubmed ID | |
Authors |
Matthias Lechner, Garrett M Frampton, Tim Fenton, Andrew Feber, Gary Palmer, Amrita Jay, Nischalan Pillay, Martin Forster, Maureen T Cronin, Doron Lipson, Vincent A Miller, Timothy A Brennan, Stephen Henderson, Francis Vaz, Paul O'Flynn, Nicholas Kalavrezos, Roman Yelensky, Stephan Beck, Philip J Stephens, Chris Boshoff |
Abstract |
Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach. Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings. HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors. These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV- disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT, and mTOR inhibitors in HNSCC. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 2 | 40% |
United States | 1 | 20% |
Unknown | 2 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 3 | 60% |
Scientists | 2 | 40% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Denmark | 2 | <1% |
Brazil | 1 | <1% |
Uruguay | 1 | <1% |
Spain | 1 | <1% |
Poland | 1 | <1% |
Unknown | 196 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 44 | 22% |
Researcher | 27 | 13% |
Student > Master | 27 | 13% |
Student > Bachelor | 16 | 8% |
Student > Doctoral Student | 14 | 7% |
Other | 38 | 19% |
Unknown | 36 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 70 | 35% |
Agricultural and Biological Sciences | 40 | 20% |
Biochemistry, Genetics and Molecular Biology | 34 | 17% |
Computer Science | 5 | 2% |
Immunology and Microbiology | 4 | 2% |
Other | 9 | 4% |
Unknown | 40 | 20% |