An inherited mitochondrial DNA disruptive mutation shifts to homoplasmy in oncocytic tumor cells

Giuseppe Gasparre, Luisa Iommarini, Anna Maria Porcelli, Martin Lang, Gian Gaetano Ferri, Ivana Kurelac, Roberta Zuntini, Elisa Mariani, Lucia Fiammetta Pennisi, Ernesto Pasquini, Gianandrea Pasquinelli, Anna Ghelli, Elena Bonora, Claudio Ceccarelli, Michela Rugolo, Nunzio Salfi, Giovanni Romeo, Valerio Carelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)391-396
Number of pages6
JournalHuman Mutation
Volume30
Issue number3
DOIs
Publication statusPublished - Mar 2009

Keywords

  • Complex I subunits
  • Disruptive mutations
  • Mitochondrial DNA
  • mtDNA
  • ND1
  • ND5
  • ND6
  • Oncocytic

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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