title: mtDNA mutations in tumors of the central nervous system reflect the neutral evolution of mtDNA in populations.
abstract: Mitochondrial DNA (mtDNA) instability has been observed in different types of cancer, including colorectal, breast, and gastric cancer. The relationship between the occurrence of such alteration and the nuclear microsatellite instability (nMI) status of the neoplastic cells remains controversial. In an attempt to clarify this issue, we sequenced the first and second mtDNA hypervariable regions, and typed the mitochondrial (CA)(n) dinucleotide polymorphism in 69 patients with primary tumors of the central nervous system (CNS), previously screened for nMI. Tumor samples showed 27 D-loop sequence changes (39.1%) compared to the corresponding blood samples. Microsatellite homoplasmic allele mutations were detected in four cases (5.8%). We did not find significant associations of the mtDNA instability status with clinicopathological parameters including sex, age, tumor size, and duration of clinical course. Neither did we find any association between mtDNA and nuclear instabilities, indicating that, at least in CNS tumors, they respond to different DNA repair mechanisms. We have also compiled the mtDNA instabilities previously reported by other authors for several types of tumors, comparing them to mtDNA polymorphisms in human populations. Most of the tumor-associated changes are common human polymorphisms and mutational hotspots. To explain the molecular behavior of mtDNA instability in tumors, we propose a model also common to other biological situations.
authors.affiliation: Unidad de Medicina Molecular, Hospital Clinico Universitario Universidad de Santiago de Compostela, Galicia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Antonio
authors.initials: A
authors.lastname: Salas
authors.forename: Elena
authors.initials: E
authors.lastname: Gamborino
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Sobrido
authors.forename: Vincent
authors.initials: V
authors.lastname: Macaulay
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
mesh_terms: D016543:Central Nervous System Neoplasms / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D005910:Glioma / Q000235:genetics; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics; D008579:Meningioma / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D009442:Neurilemmoma / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial