High Mitochondrial DNA Stability in B-Cell Chronic Lymphocytic Leukemia
dc.contributor.author | Cerezo, María | |
dc.contributor.author | Bandelt, Hans-Jürgen | |
dc.contributor.author | Martín Guerrero, Idoia | |
dc.contributor.author | Ardanaz, Maite | |
dc.contributor.author | Vega, Ana | |
dc.contributor.author | Carracedo, Angel | |
dc.contributor.author | García-Orad Carles, África | |
dc.contributor.author | Salas, Antonio | |
dc.date.accessioned | 2019-03-08T16:38:04Z | |
dc.date.available | 2019-03-08T16:38:04Z | |
dc.date.issued | 2009-11-18 | |
dc.identifier.citation | PLOS ONE 4(11) : (2009) // e7902 | es_ES |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/31947 | |
dc.description.abstract | Background: Chronic Lymphocytic Leukemia (CLL) leads to progressive accumulation of lymphocytes in the blood, bone marrow, and lymphatic tissues. Previous findings have suggested that the mtDNA could play an important role in CLL. Methodology/Principal Findings: The mitochondrial DNA (mtDNA) control-region was analyzed in lymphocyte cell DNA extracts and compared with their granulocyte counterpart extract of 146 patients suffering from B-Cell CLL; B-CLL (all recruited from the Basque country). Major efforts were undertaken to rule out methodological artefacts that would render a high false positive rate for mtDNA instabilities and thus lead to erroneous interpretation of sequence instabilities. Only twenty instabilities were finally confirmed, most of them affecting the homopolymeric stretch located in the second hypervariable segment (HVS-II) around position 310, which is well known to constitute an extreme mutational hotspot of length polymorphism, as these mutations are frequently observed in the general human population. A critical revision of the findings in previous studies indicates a lack of proper methodological standards, which eventually led to an overinterpretation of the role of the mtDNA in CLL tumorigenesis. Conclusions/Significance: Our results suggest that mtDNA instability is not the primary causal factor in B-CLL. A secondary role of mtDNA mutations cannot be fully ruled out under the hypothesis that the progressive accumulation of mtDNA instabilities could finally contribute to the tumoral process. Recommendations are given that would help to minimize erroneous interpretation of sequencing results in mtDNA studies in tumorigenesis. | es_ES |
dc.description.sponsorship | Two grants from Fundación de Investigación Médica Mutua Madrileña (2006/CL370 and 2008/CL444), a grant “Grupos Emerxentes” from Xunta de Galicia (2008/XA122), and a grant from the Ministerio de Ciencia e Innovación (SAF2008-02971) awarded to A.S. supported this project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Public Library Science | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | single hair roots | es_ES |
dc.subject | myelodysplastic syndromes | es_ES |
dc.subject | sequence variation | es_ES |
dc.subject | mtDNA mutations | es_ES |
dc.subject | haplogroup-H | es_ES |
dc.subject | near-eastern | es_ES |
dc.subject | heteroplasmy | es_ES |
dc.subject | population | es_ES |
dc.subject | disease | es_ES |
dc.subject | transplantation | es_ES |
dc.title | High Mitochondrial DNA Stability in B-Cell Chronic Lymphocytic Leukemia | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2009 Cerezo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007902 | es_ES |
dc.identifier.doi | 10.1371/journal.pone.0007902 | |
dc.departamentoes | Genética, antropología física y fisiología animal | es_ES |
dc.departamentoeu | Genetika,antropologia fisikoa eta animalien fisiologia | es_ES |
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Except where otherwise noted, this item's license is described as © 2009 Cerezo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.