title: Somatic mitochondrial DNA mutations in adult-onset leukaemia.
abstract: Mitochondrial genome instability has recently been demonstrated in a wide variety of human tumours and is implicated in the development of the myelodysplastic syndromes, a heterogeneous group of haematological disorders with an increased risk of malignant transformation. We therefore investigated the incidence of somatic mitochondrial DNA (mtDNA) mutations in patients with adult-onset leukaemia. We sequenced the entire mitochondrial genome from both normal tissue (buccal epithelial cells) and the leukaemia from 24 patients with adult-onset leukaemia. Somatic mtDNA mutation was present in nine individuals ( approximately 40%) and in each case the tumour genome differed from the normal genome sequence by a single sequence change. Using PCR-RFLP analysis and real-time PCR, we have studied in detail the mutation present in one patient with acute lymphatic leukaemia, demonstrating that the mutation is associated specifically with the leukaemia.
authors.affiliation: Mitochondrial Research Group, School of Neurology, Neurobiology and Psychiatry, The Medical School, University of Newcastle upon Tyne, UK.
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: L
authors.initials: L
authors.lastname: Luo
authors.forename: S J
authors.initials: SJ
authors.lastname: Proctor
authors.forename: P G
authors.initials: PG
authors.lastname: Middleton
authors.forename: E L
authors.initials: EL
authors.lastname: Blakely
authors.forename: R W
authors.initials: RW
authors.lastname: Taylor
authors.forename: D M
authors.initials: DM
authors.lastname: Turnbull
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial