title: High mitochondrial DNA stability in B-cell chronic lymphocytic leukemia.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Unidade de Xenética, Instituto de Medicina Legal, and Departamento de Anatomía Patolóxica y Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Cerezo
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Bandelt
authors.forename: Idoia
authors.initials: I
authors.lastname: Martín-Guerrero
authors.forename: Maite
authors.initials: M
authors.lastname: Ardanaz
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Africa
authors.initials: A
authors.lastname: García-Orad
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
mesh_terms: D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D030541:Databases, Genetic; D006098:Granulocytes / Q000166:cytology; D006239:Haplotypes; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology; D015233:Models, Statistical; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial