Fusobacterium in colonic flora and molecular features of colorectal carcinoma

Tomomitsu Tahara, Eiichiro Yamamoto, Hiromu Suzuki, Reo Maruyama, Woonbok Chung, Judith Garriga, Jaroslav Jelinek, Hiro O. Yamano, Tamotsu Sugai, Byonggu An, Imad Shureiqi, Minoru Toyota, Yutaka Kondo, Marcos R.H. Estecio, Jean Pierre J. Issa

Research output: Contribution to journalArticle

160 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1311-1318
Number of pages8
JournalCancer Research
Volume74
Issue number5
DOIs
Publication statusPublished - 01-03-2014

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Fusobacterium
Colorectal Neoplasms
Exome
Microsatellite Instability
Mucous Membrane
CpG Islands
Mutation
Phenotype
Colonic Neoplasms
Methylation
Real-Time Polymerase Chain Reaction
Neoplasms
Bacteria

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tahara, T., Yamamoto, E., Suzuki, H., Maruyama, R., Chung, W., Garriga, J., ... Issa, J. P. J. (2014). Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Research, 74(5), 1311-1318. https://doi.org/10.1158/0008-5472.CAN-13-1865
Tahara, Tomomitsu ; Yamamoto, Eiichiro ; Suzuki, Hiromu ; Maruyama, Reo ; Chung, Woonbok ; Garriga, Judith ; Jelinek, Jaroslav ; Yamano, Hiro O. ; Sugai, Tamotsu ; An, Byonggu ; Shureiqi, Imad ; Toyota, Minoru ; Kondo, Yutaka ; Estecio, Marcos R.H. ; Issa, Jean Pierre J. / Fusobacterium in colonic flora and molecular features of colorectal carcinoma. In: Cancer Research. 2014 ; Vol. 74, No. 5. pp. 1311-1318.
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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.",
author = "Tomomitsu Tahara and Eiichiro Yamamoto and Hiromu Suzuki and Reo Maruyama and Woonbok Chung and Judith Garriga and Jaroslav Jelinek and Yamano, {Hiro O.} and Tamotsu Sugai and Byonggu An and Imad Shureiqi and Minoru Toyota and Yutaka Kondo and Estecio, {Marcos R.H.} and Issa, {Jean Pierre J.}",
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Tahara, T, Yamamoto, E, Suzuki, H, Maruyama, R, Chung, W, Garriga, J, Jelinek, J, Yamano, HO, Sugai, T, An, B, Shureiqi, I, Toyota, M, Kondo, Y, Estecio, MRH & Issa, JPJ 2014, 'Fusobacterium in colonic flora and molecular features of colorectal carcinoma', Cancer Research, vol. 74, no. 5, pp. 1311-1318. https://doi.org/10.1158/0008-5472.CAN-13-1865

Fusobacterium in colonic flora and molecular features of colorectal carcinoma. / Tahara, Tomomitsu; Yamamoto, Eiichiro; Suzuki, Hiromu; Maruyama, Reo; Chung, Woonbok; Garriga, Judith; Jelinek, Jaroslav; Yamano, Hiro O.; Sugai, Tamotsu; An, Byonggu; Shureiqi, Imad; Toyota, Minoru; Kondo, Yutaka; Estecio, Marcos R.H.; Issa, Jean Pierre J.

In: Cancer Research, Vol. 74, No. 5, 01.03.2014, p. 1311-1318.

Research output: Contribution to journalArticle

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T1 - Fusobacterium in colonic flora and molecular features of colorectal carcinoma

AU - Tahara, Tomomitsu

AU - Yamamoto, Eiichiro

AU - Suzuki, Hiromu

AU - Maruyama, Reo

AU - Chung, Woonbok

AU - Garriga, Judith

AU - Jelinek, Jaroslav

AU - Yamano, Hiro O.

AU - Sugai, Tamotsu

AU - An, Byonggu

AU - Shureiqi, Imad

AU - Toyota, Minoru

AU - Kondo, Yutaka

AU - Estecio, Marcos R.H.

AU - Issa, Jean Pierre J.

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N2 - 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.

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