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Titolo:
High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection
Autore:
Coller, HA; Khrapko, K; Bodyak, ND; Nekhaeva, E; Herrero-Jimenez, P; Thilly, WG;
Indirizzi:
Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98119 USA Fred Hutchinson Canc Res Ctr Seattle WA USA 98119 , Seattle, WA 98119 USA Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA Beth Israel Deaconess Med Ctr Boston MA USA 02115 r, Boston, MA 02115 USA Harvard Univ, Sch Med, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 vard Univ, Sch Med, Boston, MA 02115 USA MIT, Div Bioengn & Environm Hlth, Environm Hlth Sci Ctr, Cambridge, MA 02139 USA MIT Cambridge MA USA 02139 Environm Hlth Sci Ctr, Cambridge, MA 02139 USA
Titolo Testata:
NATURE GENETICS
fascicolo: 2, volume: 28, anno: 2001,
pagine: 147 - 150
SICI:
1061-4036(200106)28:2<147:HFOHMD>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
MICROSATELLITE INSTABILITY; SOMATIC MUTATIONS; POINT MUTATIONS; CONTROL REGION; UNITED-STATES; COLON-CANCER; GENOME; SEGREGATION; ADVANTAGE; SEQUENCE;
Tipo documento:
Letter
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Coller, HA Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98119 USA Fred Hutchinson Canc Res Ctr Seattle WA USA 98119 WA 98119 USA
Citazione:
H.A. Coller et al., "High frequency of homoplasmic mitochondrial DNA mutations in human tumors can be explained without selection", NAT GENET, 28(2), 2001, pp. 147-150

Abstract

Researchers in several laboratories have reported a high frequency of homoplasmic mitochondrial DNA (mtDNA) mutations in human tumors(1-6). This observation has been interpreted to reflect a replicative advantage for mutatedmtDNA copies(1,2,6), a growth advantage for a cell containing certain mtDNA mutations(1,6), and/or tumorigenic properties of mtDNA mutations(2). We consider another possibility-that the observed homoplasmy arose entirely by chance in tumor progenitor cells, without any physiological advantage or tumorigenic requirement. Through extensive computer modeling, we demonstrate that there is sufficient opportunity for a tumor progenitor cell to achievehomoplasmy through unbiased mtDNA replication and sorting during cell division. To test our model in vivo, we analyzed mtDNA homoplasmy in healthy human epithelial tissues and discovered that the model correctly predicts theconsiderable observed frequency of homoplasmic cells. Based on the available data on mitochondrial mutant fractions and cell division kinetics, we show that the predicted frequency of homoplasmy in tumor progenitor cells in the absence of selection is similar to the reported frequency of homoplasmic mutations in tumors. Although a role for other mechanisms is not excluded, random processes are sufficient to explain the incidence of homoplasmic mtDNA mutations in human tumors.

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Documento generato il 26/01/20 alle ore 00:56:18