Genomic analysis identifies association of Fusobacterium with colorectal carcinoma (original) (raw)

  1. Dirk Gevers1,
  2. Chandra Sekhar Pedamallu1,3,
  3. Monia Michaud4,
  4. Fujiko Duke1,3,
  5. Ashlee M. Earl1,
  6. Akinyemi I. Ojesina1,3,
  7. Joonil Jung1,
  8. Adam J. Bass1,3,
  9. Josep Tabernero5,
  10. José Baselga5,
  11. Chen Liu6,
  12. Ramesh A. Shivdasani3,
  13. Shuji Ogino2,3,7,
  14. Bruce W. Birren1,
  15. Curtis Huttenhower1,8,
  16. Wendy S. Garrett1,3,4 and
  17. Matthew Meyerson1,2,3,9
  18. 1Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts 02142, USA;
  19. 2Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;
  20. 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;
  21. 4Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA;
  22. 5Department of Medical Oncology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain;
  23. 6Departments of Pathology, Immunology, and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida 32610, USA;
  24. 7Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;
  25. 8Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA

Abstract

The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characterized the composition of the microbiota in colorectal carcinoma using whole genome sequences from nine tumor/normal pairs. Fusobacterium sequences were enriched in carcinomas, confirmed by quantitative PCR and 16S rDNA sequence analysis of 95 carcinoma/normal DNA pairs, while the Bacteroidetes and Firmicutes phyla were depleted in tumors. Fusobacteria were also visualized within colorectal tumors using FISH. These findings reveal alterations in the colorectal cancer microbiota; however, the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation.

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