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Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a very common and mostly incurable B-cell malignancy. Recent studies revealed high interpatient mutational heterogeneity and worsened therapy response and survival of patients with complex genomic aberrations. In line with this, a better understanding of the und...

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Autores principales: Akimova, Ekaterina, Gassner, Franz Josef, Greil, Richard, Zaborsky, Nadja, Geisberger, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835664/
https://www.ncbi.nlm.nih.gov/pubmed/35163016
http://dx.doi.org/10.3390/ijms23031094
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author Akimova, Ekaterina
Gassner, Franz Josef
Greil, Richard
Zaborsky, Nadja
Geisberger, Roland
author_facet Akimova, Ekaterina
Gassner, Franz Josef
Greil, Richard
Zaborsky, Nadja
Geisberger, Roland
author_sort Akimova, Ekaterina
collection PubMed
description Chronic lymphocytic leukemia (CLL) is a very common and mostly incurable B-cell malignancy. Recent studies revealed high interpatient mutational heterogeneity and worsened therapy response and survival of patients with complex genomic aberrations. In line with this, a better understanding of the underlying mechanisms of specific genetic aberrations would reveal new prognostic factors and possible therapeutic targets. It is known that chromosomal rearrangements including DNA insertions often play a role during carcinogenesis. Recently it was reported that bacteria (microbiome)–human lateral gene transfer occurs in somatic cells and is enriched in cancer samples. To further investigate this mechanism in CLL, we analyzed paired-end RNA sequencing data of 45 CLL patients and 9 healthy donors, in which we particularly searched for bacterial DNA integrations into the human somatic genome. Applying the Burrows–Wheeler aligner (BWA) first on a human genome and then on bacterial genome references, we differentiated between sequencing reads mapping to the human genome, to the microbiome or to bacterial integrations into the human genome. Our results indicate that CLL samples featured bacterial DNA integrations more frequently (approx. two-fold) compared to normal samples, which corroborates the latest findings in other cancer entities. Moreover, we determined common integration sites and recurrent integrated bacterial transcripts. Finally, we investigated the contribution of bacterial integrations to oncogenesis and disease progression.
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spelling pubmed-88356642022-02-12 Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia Akimova, Ekaterina Gassner, Franz Josef Greil, Richard Zaborsky, Nadja Geisberger, Roland Int J Mol Sci Article Chronic lymphocytic leukemia (CLL) is a very common and mostly incurable B-cell malignancy. Recent studies revealed high interpatient mutational heterogeneity and worsened therapy response and survival of patients with complex genomic aberrations. In line with this, a better understanding of the underlying mechanisms of specific genetic aberrations would reveal new prognostic factors and possible therapeutic targets. It is known that chromosomal rearrangements including DNA insertions often play a role during carcinogenesis. Recently it was reported that bacteria (microbiome)–human lateral gene transfer occurs in somatic cells and is enriched in cancer samples. To further investigate this mechanism in CLL, we analyzed paired-end RNA sequencing data of 45 CLL patients and 9 healthy donors, in which we particularly searched for bacterial DNA integrations into the human somatic genome. Applying the Burrows–Wheeler aligner (BWA) first on a human genome and then on bacterial genome references, we differentiated between sequencing reads mapping to the human genome, to the microbiome or to bacterial integrations into the human genome. Our results indicate that CLL samples featured bacterial DNA integrations more frequently (approx. two-fold) compared to normal samples, which corroborates the latest findings in other cancer entities. Moreover, we determined common integration sites and recurrent integrated bacterial transcripts. Finally, we investigated the contribution of bacterial integrations to oncogenesis and disease progression. MDPI 2022-01-20 /pmc/articles/PMC8835664/ /pubmed/35163016 http://dx.doi.org/10.3390/ijms23031094 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Akimova, Ekaterina
Gassner, Franz Josef
Greil, Richard
Zaborsky, Nadja
Geisberger, Roland
Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia
title Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia
title_full Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia
title_fullStr Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia
title_full_unstemmed Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia
title_short Detecting Bacterial–Human Lateral Gene Transfer in Chronic Lymphocytic Leukemia
title_sort detecting bacterial–human lateral gene transfer in chronic lymphocytic leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835664/
https://www.ncbi.nlm.nih.gov/pubmed/35163016
http://dx.doi.org/10.3390/ijms23031094
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