An inherited mitochondrial DNA disruptive mutation shifts to homoplasmy in oncocytic tumor cells.
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.
Gasparre
Giuseppe
G
Unità di Genetica Medica, Policlinico Universitario S. Orsola-Malpighi, Bologna, Italy.
Iommarini
Luisa
L
Porcelli
Anna Maria
AM
Lang
Martin
M
Ferri
Gian Gaetano
GG
Kurelac
Ivana
I
Zuntini
Roberta
R
Mariani
Elisa
E
Pennisi
Lucia Fiammetta
LF
Pasquini
Ernesto
E
Pasquinelli
Gianandrea
G
Ghelli
Anna
A
Bonora
Elena
E
Ceccarelli
Claudio
C
Rugolo
Michela
M
Salfi
Nunzio
N
Romeo
Giovanni
G
Carelli
Valerio
V
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
D004272:DNA, Mitochondrial; D042967:Electron Transport Complex I