The epigenetic landscape of oral squamous cell carcinoma

Puthen V. Jithesh, J. M. Risk, A. G. Schache, J. Dhanda, B. Lane, T. Liloglou, R. J. Shaw

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Background:There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs.Methods:DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival.Results:Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between 'CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series.Conclusion:Although OSCC seems as much an 'epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.

Original languageEnglish
Pages (from-to)370-379
Number of pages10
JournalBritish Journal of Cancer
Volume108
Issue number2
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Fingerprint

Epigenomics
Methylation
Squamous Cell Carcinoma
Papillomaviridae
CpG Islands
Recurrence
Phenotype
Neoplasms
Inborn Genetic Diseases
DNA
DNA Methylation
Genes
Mucous Membrane
Biomarkers
Mutation

Keywords

  • DNA methylation
  • Microarray
  • Oral squamous cell carcinoma
  • Prognosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Jithesh, P. V., Risk, J. M., Schache, A. G., Dhanda, J., Lane, B., Liloglou, T., & Shaw, R. J. (2013). The epigenetic landscape of oral squamous cell carcinoma. British Journal of Cancer, 108(2), 370-379. https://doi.org/10.1038/bjc.2012.568

The epigenetic landscape of oral squamous cell carcinoma. / Jithesh, Puthen V.; Risk, J. M.; Schache, A. G.; Dhanda, J.; Lane, B.; Liloglou, T.; Shaw, R. J.

In: British Journal of Cancer, Vol. 108, No. 2, 02.2013, p. 370-379.

Research output: Contribution to journalArticle

Jithesh, PV, Risk, JM, Schache, AG, Dhanda, J, Lane, B, Liloglou, T & Shaw, RJ 2013, 'The epigenetic landscape of oral squamous cell carcinoma', British Journal of Cancer, vol. 108, no. 2, pp. 370-379. https://doi.org/10.1038/bjc.2012.568
Jithesh PV, Risk JM, Schache AG, Dhanda J, Lane B, Liloglou T et al. The epigenetic landscape of oral squamous cell carcinoma. British Journal of Cancer. 2013 Feb;108(2):370-379. https://doi.org/10.1038/bjc.2012.568
Jithesh, Puthen V. ; Risk, J. M. ; Schache, A. G. ; Dhanda, J. ; Lane, B. ; Liloglou, T. ; Shaw, R. J. / The epigenetic landscape of oral squamous cell carcinoma. In: British Journal of Cancer. 2013 ; Vol. 108, No. 2. pp. 370-379.
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