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Titolo:
Mitochondrial genome instability in human cancers
Autore:
Bianchi, NO; Bianchi, MS; Richard, SM;
Indirizzi:
IMBICE, RA-1900 La Plata, Argentina IMBICE La Plata Argentina RA-1900IMBICE, RA-1900 La Plata, Argentina
Titolo Testata:
MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH
fascicolo: 1, volume: 488, anno: 2001,
pagine: 9 - 23
SICI:
1383-5742(200103)488:1<9:MGIIHC>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
MTDNA CONTROL REGION; CYTOCHROME-C-OXIDASE; DNA-POLYMERASE-GAMMA; MICROSATELLITE INSTABILITY; D-LOOP; COLORECTAL CARCINOMAS; NUCLEOTIDE-SEQUENCE; SOMATIC MUTATIONS; BASE SUBSTITUTION; POINT MUTATIONS;
Keywords:
mitochondrial mutations; mitochondria; cancer; generic instability;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
108
Recensione:
Indirizzi per estratti:
Indirizzo: Bianchi, NO IMBICE, CC 403, RA-1900 La Plata, Argentina IMBICE CC 403 La Plata Argentina RA-1900 La Plata, Argentina
Citazione:
N.O. Bianchi et al., "Mitochondrial genome instability in human cancers", MUT RES-R M, 488(1), 2001, pp. 9-23

Abstract

Malfunction of mismatch repair (MMR) genes produces nuclear genome instability (NGI) and plays an important role in the origin of some hereditary andsporadic human cancers. The appearance of non-inherited microsatellite alleles in tumor cells (microsatellite instability, MSI) is one of the expressions of NGI. We present here data showing mitochondrial genome instability (mtGI) in most of the human cancers analyzed so far. The mtDNA markers usedwere point mutations, length-tract instability of mono- or dinucleotide repeats, mono- or dinucleotide insertions or deletions, and long deletions. Comparison of normal and tumoral tissues from the same individual reveals that mt-mutations may show as homoplasmic (all tumor cells have the same variant haplotype) or as heteroplasmic (tumor cells are a mosaic of inherited and acquired variant haplotypes). Breast, colorectal, gastric and kidney cancers exhibit mtGI with a pattern of mt-mutations specific for each tumor. No correlation between NGI and mtGI was found in breast, colorectal or kidney cancers, while a positive correlation was found in gastric cancer. Conversely, germ cell testicular cancers lack mtGI. Damage by reactive oxygen species (ROS), slipped-strand mispairing (SSM) and deficient repair are the causes explaining the appearance of mtGI. The replication and repair of mtDNAare controlled by nuclear genes. So far, there is no clear evidence linking MMR gene malfunction with mtGI. Polymerase gamma (POL gamma) carries out the mtDNA synthesis. Since this process is error-prone due to a deficiency in the proofreading activity of POL gamma, this enzyme has been assumed to be involved in the origin of mt-mutations. Somatic cells have hundreds to thousands of mtDNA molecules with a very high rate of spontaneous mutations. Accordingly, most somatic cells probably have a low frequency of randomly mutated mtDNA molecules. Most cancers are of monoclonal origin. Hence, to explain the appearance of mtGI in tumors we have to explain why a given variant mt-haplotype expands and replaces part of (heteroplasmy) or all (homoplasmy) wild mt-haplotypes in cancer cells. Selective and/or replicative advantage of some mutations combined with a severe bottleneck during the mitochondrial segregation accompanying mitosis are the mechanisms probably involved in the origin of mtGI. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 07:28:58