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

    4 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.
    LanguageEnglish
    Article number53
    Pages1-14
    Number of pages14
    JournalGenome Medicine
    Volume9
    Early online date7 Jun 2017
    DOIs
    Publication statusE-pub ahead of print - 7 Jun 2017

    Fingerprint

    Mouth Neoplasms
    Genome
    Carcinoma
    Mutation
    Neoplasms
    Exome
    Mutation Rate
    Early Detection of Cancer
    Clone Cells
    Population
    Genes
    Therapeutics

    Keywords

    • Pre-cancer
    • oral cancer
    • tumour progression

    Cite this

    Wood, Henry ; Daly, Catherine ; Chalkley, Rebecca ; Senguven, Burcu ; Ross, Lisa ; Egan, Philip ; Chengot, Preetha ; Graham, Jennifer ; Sethi, Neeraj ; Ong, Thian K ; MacLennan, Kenneth ; Rabbitts, Pamela ; Conway, Caroline. / The genomic road to invasion - examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples. In: Genome Medicine. 2017 ; Vol. 9. pp. 1-14.
    @article{2e69c98256bf467fb362dda935a520b1,
    title = "The genomic road to invasion - examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples.",
    abstract = "BackgroundIt 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.MethodsWe 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.ResultsEvidence 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.ConclusionsThese 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.",
    keywords = "Pre-cancer, oral cancer, tumour progression",
    author = "Henry Wood and Catherine Daly and Rebecca Chalkley and Burcu Senguven and Lisa Ross and Philip Egan and Preetha Chengot and Jennifer Graham and Neeraj Sethi and Ong, {Thian K} and Kenneth MacLennan and Pamela Rabbitts and Caroline Conway",
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    doi = "10.1186/s13073-017-0442-0",
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    Wood, H, Daly, C, Chalkley, R, Senguven, B, Ross, L, Egan, P, Chengot, P, Graham, J, Sethi, N, Ong, TK, 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, vol. 9, 53, pp. 1-14. https://doi.org/10.1186/s13073-017-0442-0

    The genomic road to invasion - examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples. / Wood, Henry; Daly, Catherine; Chalkley, Rebecca; Senguven, Burcu; Ross, Lisa; Egan, Philip; Chengot, Preetha; Graham, Jennifer; Sethi, Neeraj; Ong, Thian K; MacLennan, Kenneth; Rabbitts, Pamela; Conway, Caroline.

    In: Genome Medicine, Vol. 9, 53, 07.06.2017, p. 1-14.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The genomic road to invasion - examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples.

    AU - Wood, Henry

    AU - Daly, Catherine

    AU - Chalkley, Rebecca

    AU - Senguven, Burcu

    AU - Ross, Lisa

    AU - Egan, Philip

    AU - Chengot, Preetha

    AU - Graham, Jennifer

    AU - Sethi, Neeraj

    AU - Ong, Thian K

    AU - MacLennan, Kenneth

    AU - Rabbitts, Pamela

    AU - Conway, Caroline

    PY - 2017/6/7

    Y1 - 2017/6/7

    N2 - BackgroundIt 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.MethodsWe 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.ResultsEvidence 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.ConclusionsThese 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.

    AB - BackgroundIt 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.MethodsWe 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.ResultsEvidence 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.ConclusionsThese 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.

    KW - Pre-cancer

    KW - oral cancer

    KW - tumour progression

    U2 - 10.1186/s13073-017-0442-0

    DO - 10.1186/s13073-017-0442-0

    M3 - Article

    VL - 9

    SP - 1

    EP - 14

    JO - Genome Medicine

    T2 - Genome Medicine

    JF - Genome Medicine

    SN - 1756-994X

    M1 - 53

    ER -