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Titolo:
Thyroid carcinoma is characterized by genomic instability: Evidence from p53 mutations
Autore:
Shahedian, B; Shi, YF; Zou, MJ; Farid, NR;
Indirizzi:
Oscancor Biotech Inc, Watford WD17 3BY, Herts, England Oscancor Biotech Inc Watford Herts England WD17 3BY 7 3BY, Herts, England King Faisal Specialist Hosp & Res Ctr, Dept Biomed Res, Riyadh 11211, Saudi Arabia King Faisal Specialist Hosp & Res Ctr Riyadh Saudi Arabia 11211 i Arabia Hemel Hempstead Gen Hosp, Dept Endocrinol, Hemel Hempstead, Herts, EnglandHemel Hempstead Gen Hosp Hemel Hempstead Herts England d, Herts, England
Titolo Testata:
MOLECULAR GENETICS AND METABOLISM
fascicolo: 2, volume: 72, anno: 2001,
pagine: 155 - 163
SICI:
1096-7192(200102)72:2<155:TCICBG>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-SUPPRESSOR GENES; MOLECULAR PATHOGENESIS; CANCER; RADIATION; CELLS; RAS; ASSOCIATION; PREVALENCE; CHILDREN; ACCIDENT;
Keywords:
thyroid cancer; p53; mutation; genomic instability; radiation; epigenetic; CpG deamination; differentiation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Farid, NR Oscancor Biotech Inc, 31 Woodland Dr, Watford WD17 3BY, Herts, England Oscancor Biotech Inc 31 Woodland Dr Watford Herts England WD17 3BY
Citazione:
B. Shahedian et al., "Thyroid carcinoma is characterized by genomic instability: Evidence from p53 mutations", MOL GEN MET, 72(2), 2001, pp. 155-163

Abstract

p53 is a transcription factor with multifaceted regulatory functions in cell cycle progression, DNA repair, and programmed cell death. Inactivating mutations have been described in 50% of human cancers. These mutations appear to be important in tumor progression and response to chemotherapy and radiation treatment and thus clinical outcome. p53 mutations are found in 14% of malignant thyroid tumors and are more frequent in poorly differentiated and anaplastic tumors. Given that p53 is a late event in the notional multistep pathogenesis of cancer, we examined its mutation rates as a measure ofgenomic instability (hypermutability) of malignant thyroid tumors and alsowondered whether radiation enhances that proclivity to genomic instability. To that end we have extracted all available data from the p53 mutation database (http:// www.perso@curie.fr), verified, extended, where applicable, and supplemented that information from published reports. We were able to identify 100 entries. The distribution of the p53 mutational events-deletions/insertions, transitions versus transversion mutations-as similar to that of the database as a whole. The silent mutation rate of 17.8%, not different from the expected 25%, is consistent with a random occurrence of these mutations. The silent mutation rate is 120 times that expected and is 6 timesthat of the database. Moreover, the distribution of p53 mutations is compatible with Poisson's distribution, which taken with silent mutation rates indicates that p53 is particularly hypermutable in thyroid carcinomas. Epigenetic deamination of CpG dinucleotide at highly oncogenic DNA-contact residues is a feature of poorly differentiated tumors and thus associated with tumor progression. The rates of p53 mutations (15.4%) in radiation-related cancers were very similar to those in apparently spontaneously arising tumors, although there was a highly significant heterogeneity (P < 0.0005) in the residues mutated. None involved CpG deamination. It is apparent that thyroid cancer exhibits remarkable genomic instabilityevidenced by p53 hypermutability. Spontaneous epigenetic mutational eventsare involved in tumor progression and while radiation increases the absolute prevalence of thyroid cancer in the susceptible it does not increase therate of p53 mutation and seemingly targets different non-DNA-contact residues than those in spontaneously arising tumors. (C) 2001 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 18:42:24