Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma

  1. Robert A. Holt1,2,7
  1. 1BC Cancer Agency, Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada;
  2. 2Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada;
  3. 3University of Guelph, Guelph, Ontario N1G 2W1, Canada;
  4. 4BC Cancer Agency, Deeley Research Centre, Victoria, British Columbia V8R 6V5, Canada;
  5. 5Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada
    1. 6 These authors contributed equally to this work.

    Abstract

    An estimated 15% or more of the cancer burden worldwide is attributable to known infectious agents. We screened colorectal carcinoma and matched normal tissue specimens using RNA-seq followed by host sequence subtraction and found marked over-representation of Fusobacterium nucleatum sequences in tumors relative to control specimens. F. nucleatum is an invasive anaerobe that has been linked previously to periodontitis and appendicitis, but not to cancer. Fusobacteria are rare constituents of the fecal microbiota, but have been cultured previously from biopsies of inflamed gut mucosa. We obtained a Fusobacterium isolate from a frozen tumor specimen; this showed highest sequence similarity to a known gut mucosa isolate and was confirmed to be invasive. We verified overabundance of Fusobacterium sequences in tumor versus matched normal control tissue by quantitative PCR analysis from a total of 99 subjects (p = 2.5 × 10−6), and we observed a positive association with lymph node metastasis.

    Footnotes

    • Received May 20, 2011.
    • Accepted July 29, 2011.

    Freely available online through the Genome Research Open Access option.

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