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pmid:23840181

Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples.

David R Riley · Karsten B Sieber · Kelly M Robinson · James Robert White · Ashwinkumar Ganesan · Syrus Nourbakhsh · Julie C Dunning Hotopp

PLoS computational biology · 2013 doi:10.1371/journal.pcbi.1003107

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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title
Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples.
doi
10.1371/journal.pcbi.1003107
pmid
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David R Riley
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Karsten B Sieber
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Kelly M Robinson
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James Robert White
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Ashwinkumar Ganesan
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Syrus Nourbakhsh
[6]
Julie C Dunning Hotopp
journal
PLoS computational biology
year
2013
abstract
There are 10× more bacterial cells in our bodies from the microbiome than human cells. Viral DNA is known to integrate in the human genome, but the integration of bacterial DNA has not been described. Using publicly available sequence data from the human genome project, the 1000 Genomes Project, and The Cancer Genome Atlas (TCGA), we examined bacterial DNA integration into the human somatic genome. Here we present evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, and that such integrations are detected more frequently in (a) tumors than normal samples, (b) RNA than DNA samples, and (c) the mitochondrial genome than the nuclear genome. Hundreds of thousands of paired reads support random integration of Acinetobacter-like DNA in the human mitochondrial genome in acute myeloid leukemia samples. Numerous read pairs across multiple stomach adenocarcinoma samples support specific integration of Pseudomonas-like DNA in the 5'-UTR and 3'-UTR of four proto-oncogenes that are up-regulated in their transcription, consistent with conversion to an oncogene. These data support our hypothesis that bacterial integrations occur in the human somatic genome and may play a role in carcinogenesis. We anticipate that the application of our approach to additional cancer genome projects will lead to the more frequent detection of bacterial DNA integrations in tumors that are in close proximity to the human microbiome.
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Reads supporting bacterial DNA integration were detected more frequently in the human mitochondrial genome (Figure 6A, 41,852 reads in 16.6 kbp) than in the human nuclear genome (48,874 reads in 2.86 Gbp; p<2×10−16, Chi-squared test).
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Reads supporting bacterial DNA integration were detected more frequently in the human mitochondrial genome (Figure 6A, 41,852 reads in 16.6 kbp) than in the human nuclear genome (48,874 reads in 2.86 Gbp; p<2×10−16, Chi-squared test).
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sections[23] "Analysis of Illumina data from the TCGA" paragraph 2
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Reads supporting bacterial DNA integration were detected more frequently in the human mitochondrial genome (Figure 6A, 41,852 reads in 16.6 kbp) than in the human nuclear genome (48,874 reads in 2.86 Gbp; p<2×10−16, Chi-squared test).
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Viral DNA is known to integrate in the human genome, but the integration of bacterial DNA has not been described. Using publicly available sequence data from the human genome project, the 1000 Genomes Project, and The Cancer Genome Atlas (TCGA), we examined bacterial DNA integration into the human somatic genome. Here we present evidence that bacterial DNA integrates into the human somatic genome through an RNA intermediate, and that such integrations are detected more frequently in (a) tumors than normal samples, (b) RNA than DNA samples, and (c) the mitochondrial genome than the nuclear genome. Hundreds of thousands of paired reads support random integration of Acinetobacter-like DNA in the human mitochondrial genome in acute myeloid leukemia samples. 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