TY - JOUR
T1 - Colorectal cancer mutational profiles correlate with defined microbial communities in the tumor microenvironment
AU - Burns, Michael B.
AU - Montassier, Emmanuel
AU - Abrahante, Juan
AU - Priya, Sambhawa
AU - Niccum, David E.
AU - Khoruts, Alexander
AU - Starr, Timothy K.
AU - Knights, Dan
AU - Blekhman, Ran
N1 - Publisher Copyright:
© 2018 Burns et al. http://creativecommons.org/licenses/by/4.0/
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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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U2 - 10.1371/journal.pgen.1007376
DO - 10.1371/journal.pgen.1007376
M3 - Article
C2 - 29924794
AN - SCOPUS:85049446291
SN - 1553-7390
VL - 14
JO - PLoS genetics
JF - PLoS genetics
IS - 6
M1 - e1007376
ER -