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      The human tumor microbiome is composed of tumor type–specific intracellular bacteria

      1 , 1 , 2 , 3 , 1 , 1 , 1 , 1 , 4 , 5 , 1 , 1 , 1 , 6 , 7 , 8 , 9 , 9 , 10 , 11 , 12 , 8 , 13 , 8 , 8 , 1 , 2 , 14 , 1 , 2 , 1 , 2 , 15 , 16 , 17 , 16 , 18 , 18 , 19 , 19 , 20 , 21 , 22 , 23 , 24 , 5 , 25 , 5 , 26 , 27 , 28 , 29 , 28 , 10 , 30 , 6 , 31 , 5 , 17 , 5 , 7 , 32 , 5 , 7 , 16 , 5 , 16 , 5 , 7 , 5 , 27 , 5 , 33 , 34 , 35 , 1 , 2 , 8 , 13 , 28 , 36 , 1
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      American Association for the Advancement of Science (AAAS)

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          Abstract

          Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients’ smoking status, and the response to immunotherapy.

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          Most cited references31

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          The microbiome, cancer, and cancer therapy

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            Inherent bacterial DNA contamination of extraction and sequencing reagents may affect interpretation of microbiota in low bacterial biomass samples

            Background The advent and use of highly sensitive molecular biology techniques to explore the microbiota and microbiome in environmental and tissue samples have detected the presence of contaminating microbial DNA within reagents. These microbial DNA contaminants may distort taxonomic distributions and relative frequencies in microbial datasets, as well as contribute to erroneous interpretations and identifications. Results We herein report on the occurrence of bacterial DNA contamination within commonly used DNA extraction kits and PCR reagents and the effect of these contaminates on data interpretation. When compared to previous reports, we identified an additional 88 bacterial genera as potential contaminants of molecular biology grade reagents, bringing the total number of known contaminating microbes to 181 genera. Many of the contaminants detected are considered normal inhabitants of the human gastrointestinal tract and the environment and are often indistinguishable from those genuinely present in the sample. Conclusions Laboratories working on bacterial populations need to define contaminants present in all extraction kits and reagents used in the processing of DNA. Any unusual and/or unexpected findings need to be viewed as possible contamination as opposed to unique findings. Electronic supplementary material The online version of this article (doi:10.1186/s13099-016-0103-7) contains supplementary material, which is available to authorized users.
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              The Microbiota of Breast Tissue and Its Association with Breast Cancer

              ABSTRACT In the United States, 1 in 8 women will be diagnosed with breast cancer in her lifetime. Along with genetics, the environment contributes to disease development, but what these exact environmental factors are remains unknown. We have previously shown that breast tissue is not sterile but contains a diverse population of bacteria. We thus believe that the host's local microbiome could be modulating the risk of breast cancer development. Using 16S rRNA amplicon sequencing, we show that bacterial profiles differ between normal adjacent tissue from women with breast cancer and tissue from healthy controls. Women with breast cancer had higher relative abundances of Bacillus, Enterobacteriaceae and Staphylococcus. Escherichia coli (a member of the Enterobacteriaceae family) and Staphylococcus epidermidis, isolated from breast cancer patients, were shown to induce DNA double-stranded breaks in HeLa cells using the histone-2AX (H2AX) phosphorylation (γ-H2AX) assay. We also found that microbial profiles are similar between normal adjacent tissue and tissue sampled directly from the tumor. This study raises important questions as to what role the breast microbiome plays in disease development or progression and how we can manipulate this for possible therapeutics or prevention. IMPORTANCE This study shows that different bacterial profiles in breast tissue exist between healthy women and those with breast cancer. Higher relative abundances of bacteria that had the ability to cause DNA damage in vitro were detected in breast cancer patients, as was a decrease in some lactic acid bacteria, known for their beneficial health effects, including anticarcinogenic properties. This study raises important questions as to the role of the mammary microbiome in modulating the risk of breast cancer development.
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                Author and article information

                Journal
                Science
                Science
                American Association for the Advancement of Science (AAAS)
                0036-8075
                1095-9203
                May 28 2020
                May 29 2020
                May 28 2020
                May 29 2020
                : 368
                : 6494
                : 973-980
                Affiliations
                [1 ]Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
                [2 ]Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel.
                [3 ]Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel.
                [4 ]Division of Surgery, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
                [5 ]Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
                [6 ]Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
                [7 ]Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel.
                [8 ]Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
                [9 ]Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel.
                [10 ]Orthopaedic Pathophysiology and Regenerative Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.
                [11 ]Department of Bioinformatics, Jerusalem College of Technology, Jerusalem, Israel.
                [12 ]Translational Medicine, Oncology R&D, AstraZeneca, Gaithersburg, MD, USA.
                [13 ]Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
                [14 ]Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
                [15 ]Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.
                [16 ]Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel.
                [17 ]Department of Thoracic Surgery, Sheba Medical Center, Ramat Gan, Israel.
                [18 ]Department of Medical Oncology and Division of Molecular Oncology and Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
                [19 ]Pediatric Gastroenterology Institute, Rambam Medical Center, Haifa, Israel.
                [20 ]Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
                [21 ]Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, Israel.
                [22 ]Division of General Surgery, Rambam Health Care Campus, Haifa, Israel.
                [23 ]Ambulatory and Breast Surgery Service, Rambam Health Care Campus, Haifa, Israel.
                [24 ]Department of Thoracic Surgery, Rambam Health Care Campus, Haifa, Israel.
                [25 ]Department of Neurosurgery, Sheba Medical Center, Ramat Gan, Israel.
                [26 ]Department of Neurosurgery, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.
                [27 ]Neuro-Oncology Unit, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel.
                [28 ]Institute of Pathology, Megalab, Maccabi Healthcare Services, Rehovot, Israel.
                [29 ]Breast Oncology Institute, Sheba Medical Center, Ramat Gan, Israel.
                [30 ]Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
                [31 ]Department of Pharmacology, Dalhousie University, Halifax, NS, Canada.
                [32 ]Department of Surgical Oncology (Surgery C), Sheba Medical Center, Ramat Gan, Israel.
                [33 ]Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.
                [34 ]Division of Molecular Oncology & Immunology, Netherlands Cancer Institute, Amsterdam, Netherlands.
                [35 ]Division of Thoracic Surgery, City of Hope Medical Center, Duarte, CA, USA.
                [36 ]Department of Mathematics and Computer Science, The Open University of Israel, Ra’anana, Israel.
                Article
                10.1126/science.aay9189
                7757858
                32467386
                537823f8-5bf4-4a03-97ca-b1044c0cb620
                © 2020

                http://www.sciencemag.org/about/science-licenses-journal-article-reuse

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