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Genome Med. 2013 May 29;5(5):49. doi: 10.1186/gm453. eCollection 2013.

Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors.

Author information

  • 1UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK ; Head and Neck Centre, University College London Hospitals NHS Trust, Euston Road, London, NW1 2PG, UK.
  • 2Foundation Medicine, One Kendall Square, Suite B3501, Cambridge, MA 02139, USA.
  • 3UCL Cancer Institute, University College London, 72 Huntley Street, London, WC1E 6BT, UK.
  • 4Department of Histopathology, University College London Hospitals NHS Trust, Rockefeller Building, University Street, London, WC1E 6JJ, UK.
  • 5Head and Neck Centre, University College London Hospitals NHS Trust, Euston Road, London, NW1 2PG, UK.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

PMID:
23718828
[PubMed]
PMCID:
PMC4064312
Free PMC Article

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