title: Fusobacterium in colonic flora and molecular features of colorectal carcinoma.
abstract: Fusobacterium species are part of the gut microbiome in humans. Recent studies have identified overrepresentation of Fusobacterium in colorectal cancer tissues, but it is not yet clear whether this is pathogenic or simply an epiphenomenon. In this study, we evaluated the relationship between Fusobacterium status and molecular features in colorectal cancers through quantitative real-time PCR in 149 colorectal cancer tissues, 89 adjacent normal appearing mucosae and 72 colonic mucosae from cancer-free individuals. Results were correlated with CpG island methylator phenotype (CIMP) status, microsatellite instability (MSI), and mutations in BRAF, KRAS, TP53, CHD7, and CHD8. Whole-exome capture sequencing data were also available in 11 cases. Fusobacterium was detectable in 111 of 149 (74%) colorectal cancer tissues and heavily enriched in 9% (14/149) of the cases. As expected, Fusobacterium was also detected in normal appearing mucosae from both cancer and cancer-free individuals, but the amount of bacteria was much lower compared with colorectal cancer tissues (a mean of 250-fold lower for Pan-fusobacterium). We found the Fusobacterium-high colorectal cancer group (FB-high) to be associated with CIMP positivity (P = 0.001), TP53 wild-type (P = 0.015), hMLH1 methylation positivity (P = 0.0028), MSI (P = 0.018), and CHD7/8 mutation positivity (P = 0.002). Among the 11 cases where whole-exome sequencing data were available, two that were FB-high cases also had the highest number of somatic mutations (a mean of 736 per case in FB-high vs. 225 per case in all others). Taken together, our findings show that Fusobacterium enrichment is associated with specific molecular subsets of colorectal cancers, offering support for a pathogenic role in colorectal cancer for this gut microbiome component.
authors.affiliation: Authors' Affiliations: Fels Institute for Cancer Research & Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania; Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake; First Departments of Internal Medicine and Molecular Biology, Sapporo Medical University, Sapporo; Department of Gastroenterology, Akita Red Cross Hospital, Akita; Department of Pathology, Iwate Medical University, Morioka; Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan; Division of OVP, Department of Clinical Cancer Prevention, Cancer Prevention and Population Sciences; Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston; and Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas.
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Yamamoto
authors.forename: Hiromu
authors.initials: H
authors.lastname: Suzuki
authors.forename: Reo
authors.initials: R
authors.lastname: Maruyama
authors.forename: Woonbok
authors.initials: W
authors.lastname: Chung
authors.forename: Judith
authors.initials: J
authors.lastname: Garriga
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Jelinek
authors.forename: Hiro-o
authors.initials: HO
authors.lastname: Yamano
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sugai
authors.forename: Byonggu
authors.initials: B
authors.lastname: An
authors.forename: Imad
authors.initials: I
authors.lastname: Shureiqi
authors.forename: Minoru
authors.initials: M
authors.lastname: Toyota
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Marcos R H
authors.initials: MR
authors.lastname: Estécio
authors.forename: Jean-Pierre J
authors.initials: JP
authors.lastname: Issa
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000382:microbiology*; D018899:CpG Islands / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005673:Fusobacterium / Q000235:genetics*; D005674:Fusobacterium Infections / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009092:Mucous Membrane / Q000382:microbiology; D009154:Mutation / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: C523331:CHD8 protein, human; D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D048493:Proto-Oncogene Proteins B-raf; D004265:DNA Helicases; C491434:CHD7 protein, human; D018631:ras Proteins