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.
G.Gasparre, L. Iommarini, A.M. Porcelli, M. Lang, G.G. Ferri, I.Kurelac, et al. (2009). An inherited mitochondrial DNA disruptive mutation shifts to homoplasmy in oncocytic tumor cells. HUMAN MUTATION, 30 (3), 391-396 [10.1002/humu.20870].
An inherited mitochondrial DNA disruptive mutation shifts to homoplasmy in oncocytic tumor cells.
GASPARRE, GIUSEPPE;IOMMARINI, LUISA;PORCELLI, ANNA MARIA;FERRI, GIAN GAETANO;KURELAC, IVANA;MARIANI, ELISA;PASQUINI, ERNESTO;PASQUINELLI, GIANANDREA;GHELLI, ANNA MARIA;BONORA, ELENA;CECCARELLI, CLAUDIO;RUGOLO, MICHELA;ROMEO, GIOVANNI;CARELLI, VALERIO
2009
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
