The genomic road to invasion - examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples.

Henry Wood, Catherine Daly, Rebecca Chalkley, Burcu Senguven, Lisa Ross, Philip Egan, Preetha Chengot, Jennifer Graham, Neeraj Sethi, Thian K Ong, Kenneth MacLennan, Pamela Rabbitts, Caroline Conway

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    Abstract

    Background
    It is frequently assumed that pre-invasive lesions are simpler precursors of cancer and will contain a limited subset of the genomic changes seen in their associated invasive disease. Driver mutations are thought to occur early, but it is not known how many of these are present in pre-invasive lesions. These assumptions need to be tested with the increasing focus on both personalised cancer treatments and early detection methodologies.

    Methods
    We examined genomic copy number changes in 256 pre-invasive and invasive samples from 69 oral cancer patients. Forty-eight samples from 16 patients were further examined using exome sequencing.

    Results
    Evidence of a shared ancestor of both dysplasia and carcinoma was seen in all but one patient. One-third of dysplasias showed independent copy number events. The remainder had a copy number pattern that was similar to or simpler than that of the carcinoma. All dysplasias examined contained somatic mutations absent in the related carcinoma.

    Previously observed copy number changes and TP53 mutations were very frequently observed, and almost always shared between dysplasia and carcinoma. Other gene changes were more sporadic. Pathway analysis confirmed that each patient’s disease developed in a different way.

    Examining the numbers of shared mutations and the rate of accumulation of mutations showed evidence that all samples contain a population of sub-clones, with little evidence of selective advantage of a subset of these.

    Conclusions
    These findings suggest that most of the genomic changes driving oral cancer occur in the pre-cancerous state by way of gradual random accumulation rather than a dramatic single event.
    Original languageEnglish
    Article number53 (2017)
    Pages (from-to)1-14
    Number of pages14
    JournalGenome Medicine
    Volume9
    DOIs
    Publication statusPublished - 7 Jun 2017

    Keywords

    • Pre-cancer
    • oral cancer
    • tumour progression

    Fingerprint Dive into the research topics of 'The genomic road to invasion - examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples.'. Together they form a unique fingerprint.

  • Cite this

    Wood, H., Daly, C., Chalkley, R., Senguven, B., Ross, L., Egan, P., Chengot, P., Graham, J., Sethi, N., Ong, T. K., MacLennan, K., Rabbitts, P., & Conway, C. (2017). The genomic road to invasion - examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples. Genome Medicine, 9, 1-14. [53 (2017)]. https://doi.org/10.1186/s13073-017-0442-0