Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.

Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these...

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Main Authors: Michael B Burns, Emmanuel Montassier, Juan Abrahante, Sambhawa Priya, David E Niccum, Alexander Khoruts, Timothy K Starr, Dan Knights, Ran Blekhman
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-06-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007376&type=printable
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author Michael B Burns
Emmanuel Montassier
Juan Abrahante
Sambhawa Priya
David E Niccum
Alexander Khoruts
Timothy K Starr
Dan Knights
Ran Blekhman
author_facet Michael B Burns
Emmanuel Montassier
Juan Abrahante
Sambhawa Priya
David E Niccum
Alexander Khoruts
Timothy K Starr
Dan Knights
Ran Blekhman
author_sort Michael B Burns
collection DOAJ
description Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these changes can be used to understand microbe-host interactions with potential functional biological relevance. Here, we characterized the association between CRC microbial communities and tumor mutations using microbiome profiling and whole-exome sequencing in 44 pairs of tumors and matched normal tissues. We found statistically significant associations between loss-of-function mutations in tumor genes and shifts in the abundances of specific sets of bacterial taxa, suggestive of potential functional interaction. This correlation allows us to statistically predict interactions between loss-of-function tumor mutations in cancer-related genes and pathways, including MAPK and Wnt signaling, solely based on the composition of the microbiome. In conclusion, our study shows that CRC microbiomes are correlated with tumor mutational profiles, pointing towards possible mechanisms of molecular interaction.
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publisher Public Library of Science (PLoS)
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spelling doaj-art-ac8708ed3cde4ce6a24113c149e1c9bd2025-08-20T03:11:26ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042018-06-01146e100737610.1371/journal.pgen.1007376Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.Michael B BurnsEmmanuel MontassierJuan AbrahanteSambhawa PriyaDavid E NiccumAlexander KhorutsTimothy K StarrDan KnightsRan BlekhmanVariation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetic variation. However, we do not know whether, in addition to baseline host genetics, somatic mutational profiles in CRC tumors interact with the surrounding tumor microbiome, and if so, whether these changes can be used to understand microbe-host interactions with potential functional biological relevance. Here, we characterized the association between CRC microbial communities and tumor mutations using microbiome profiling and whole-exome sequencing in 44 pairs of tumors and matched normal tissues. We found statistically significant associations between loss-of-function mutations in tumor genes and shifts in the abundances of specific sets of bacterial taxa, suggestive of potential functional interaction. This correlation allows us to statistically predict interactions between loss-of-function tumor mutations in cancer-related genes and pathways, including MAPK and Wnt signaling, solely based on the composition of the microbiome. In conclusion, our study shows that CRC microbiomes are correlated with tumor mutational profiles, pointing towards possible mechanisms of molecular interaction.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007376&type=printable
spellingShingle Michael B Burns
Emmanuel Montassier
Juan Abrahante
Sambhawa Priya
David E Niccum
Alexander Khoruts
Timothy K Starr
Dan Knights
Ran Blekhman
Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.
PLoS Genetics
title Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.
title_full Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.
title_fullStr Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.
title_full_unstemmed Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.
title_short Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment.
title_sort colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007376&type=printable
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