title: An inherited mitochondrial DNA disruptive mutation shifts to homoplasmy in oncocytic tumor cells.
abstract: A disruptive frameshift mtDNA mutation affecting the ND5 subunit of complex I is present in homoplasmy in a nasopharyngeal oncocytic tumor and inherited as a heteroplasmic germline mutation recurring in two of the patient's siblings. Homoplasmic ND5 mutation in the tumor correlates with lack of the ND6 subunit, suggesting complex I disassembly. A few oncocytic areas, expressing ND6 and heteroplasmic for the ND5 mutation, harbor a de novo homoplasmic ND1 mutation. Since shift to homoplasmy of ND1 and ND5 mutations occurs exclusively in tumor cells, we conclude that complex I mutations may have a selective advantage and accompany oncocytic transformation.
authors.affiliation: Unità di Genetica Medica, Policlinico Universitario S. Orsola-Malpighi, Bologna, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gasparre
authors.forename: Luisa
authors.initials: L
authors.lastname: Iommarini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Porcelli
authors.forename: Martin
authors.initials: M
authors.lastname: Lang
authors.forename: Gian Gaetano
authors.initials: GG
authors.lastname: Ferri
authors.forename: Ivana
authors.initials: I
authors.lastname: Kurelac
authors.forename: Roberta
authors.initials: R
authors.lastname: Zuntini
authors.forename: Elisa
authors.initials: E
authors.lastname: Mariani
authors.forename: Lucia Fiammetta
authors.initials: LF
authors.lastname: Pennisi
authors.forename: Ernesto
authors.initials: E
authors.lastname: Pasquini
authors.forename: Gianandrea
authors.initials: G
authors.lastname: Pasquinelli
authors.forename: Anna
authors.initials: A
authors.lastname: Ghelli
authors.forename: Elena
authors.initials: E
authors.lastname: Bonora
authors.forename: Claudio
authors.initials: C
authors.lastname: Ceccarelli
authors.forename: Michela
authors.initials: M
authors.lastname: Rugolo
authors.forename: Nunzio
authors.initials: N
authors.lastname: Salfi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Romeo
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D042967:Electron Transport Complex I / Q000235:genetics* / Q000378:metabolism; D016368:Frameshift Mutation; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000648:ultrastructure; D010375:Pedigree; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D035781:Siblings
chemical_list: D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I