Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma.
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.
BC Cancer Agency, Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada.
Mauro
M
Castellarin
René L
RL
Warren
J Douglas
JD
Freeman
Lisa
L
Dreolini
Martin
M
Krzywinski
Jaclyn
J
Strauss
Rebecca
R
Barnes
Peter
P
Watson
Emma
E
Allen-Vercoe
Richard A
RA
Moore
Robert A
RA
Holt
D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015179:Colorectal Neoplasms / Q000382:microbiology*; D005674:Fusobacterium Infections / Q000382:microbiology*; D016967:Fusobacterium nucleatum / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D016680:Genome, Bacterial; D006801:Humans; D007420:Intestine, Large / Q000382:microbiology; D054892:Metagenome / Q000235:genetics; D010802:Phylogeny