Decreased copy number of mitochondrial DNA in Ewing's sarcoma |
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| Authors: | Man Yu Yanfang Wan Qinghua Zou |
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| Affiliation: | 1. Centre for Advanced Research in Environmental Genomics (CAREG), University of Ottawa, 20 Marie Curie, Ottawa, ON, Canada K1N 6N5;2. Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5;3. Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Hospital and Institute, Tianjin 300060, China;4. Department of Surgical Oncology, Central Hospital of China National Petroleum Corporation, Langfang, Hebei Province 065000, China;1. Department of Hepatopancreatobiliary Center, The Third Hospital Affiliated to Nantong University, Wuxi City, Jiangsu Province, China;2. Department of General Surgery, Huai’an Hospital Affiliated to Xuzhou Medical University, Huai''an, China;3. Department of General Surgery, The Second People’s Hospital of Wuhu, Wuhu, China;1. The Kirby Institute, UNSW Sydney, Sydney, New South Wales, Australia;2. Akershus University Hospital, Oslo, Norway;3. The Liver Unit, Queen Mary University of London, London, United Kingdom;4. Arud Centres for Addiction Medicine, Zurich, Switzerland;5. Vancouver Infectious Diseases Center, Vancouver, British Columbia, Canada;6. Ludwig Maximilians-University Munich, Munich, Germany;7. Department of Gastroenterology and Hepatology, Ziekenhuis Oost Limburg, Genk, Belgium;8. Department of Hepatology, UZ Leuven, Leuven, Belgium;9. Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium;10. International Network on Hepatitis in Substance Users, New York, NY, United States;11. Nepean Hospital, Sydney, New South Wales, Australia;12. Royal Adelaide Hospital, Adelaide, South Australia, Australia;13. School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia;14. Burnet Institute, Melbourne, Victoria, Australia;15. Research Center, Centre Hospitalier de l’Universite de Montreal (CRCHUM), Montreal, Quebec, Canada;p. Stuivenberg ZNA, Antwerp, Belgium;q. Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland;r. University of Oslo, Oslo, Norway;s. Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia;t. Department of Infectious Diseases, Akershus University Hospital, Norway;u. Institute for Clinical Medicine, University of Oslo, Norway;v. Department of Gastroenterology, Oslo University Hospital, Norway;1. Division of Surgical Oncology and Thoracic Surgery, Universitätsmedizin Mannheim, Mannheim D-68167, Germany;1. Consultant, Seattle, WA, United States;2. Payne Environmental Consultants, Inc., Encinitas, CA, United States |
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| Abstract: | BackgroundSomatic mutations and germline variations in mitochondrial DNA (mtDNA) have been widely detected in a range of human malignancies including Ewing's sarcoma (EWS). However, it still remains unknown whether quantitative alterations in mtDNA level occur during the initiation and/or progression of EWS.MethodsTo test this possibility, we determined mtDNA copy number from 17 cases of EWS tumor tissues and 5 normal bone tissue samples using a quantitative real-time PCR assay.ResultsOur results showed that the average mtDNA content was significantly reduced in cancerous specimens as compared to that in normal bone controls. mtDNA copy number was statistically associated with tumor metastasis. There was an over 2-fold decrease in tumors with metastasis than in low-grade ones without metastasis. In addition, change in mtDNA content was related to somatic mutations in the D-loop control region. Tumors harboring D-loop mutations, at the polycytidine stretch between nucleotide positions 303 and 309 or close to the replication origin sites of the heavy strand, exhibited significantly lowered mtDNA levels in comparison with those without D-loop alterations.ConclusionsThe mtDNA content reduction may be an important genetic event in the carcinogenesis of EWS. This study provides evidence that somatic D-loop mutation is likely one of the key factors contributing to quantitative changes of mtDNA in EWS. |
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