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Titolo:
P53 mutations in thyroid carcinoma: Tidings from an old foe
Autore:
Farid, NR;
Indirizzi:
Osancor Biotech Inc, Watford WD17 3BY, Herts, England Osancor Biotech IncWatford Herts England WD17 3BY 17 3BY, Herts, England
Titolo Testata:
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION
fascicolo: 7, volume: 24, anno: 2001,
pagine: 536 - 545
SICI:
0391-4097(200107/08)24:7<536:PMITCT>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-SUPPRESSOR GENES; HORMONE RECEPTOR; MOLECULAR PATHOGENESIS; HUMAN LIVER; DNA-DAMAGE; CANCER; ASSOCIATION; RADIATION; RAS; METHYLATION;
Keywords:
thyroid cancer; p53; mutations; genomic instability; radiation; epigenetic; CpG deamination; differentiation;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Farid, NR Osancor Biotech Inc, 31 Woodland Dr, Watford WD17 3BY, Herts, England Osancor Biotech Inc 31 Woodland Dr Watford Herts England WD17 3BY
Citazione:
N.R. Farid, "P53 mutations in thyroid carcinoma: Tidings from an old foe", J ENDOC INV, 24(7), 2001, pp. 536-545

Abstract

The underlying mechanism leading to carcinogenesis involves genomic instability, likely related to aneuploidy. While p53 as a "guardian of the genome" is an appealing candidate as an initiator of genomic instability, its mutations or deletions usually occur late in the course of tumor progression. P53 may, however, become a target of events initiated by genomic instability. P53 is a transcription factor with multifaceted regulatory functions in the cell cycle, DNA repair and apoptosis. Inactivating p53 mutations have been described in some 50% of human cancers. These mutations are not only important in tumor progression but apparently also in the response of some tumors to chemotherapy and radiation treatment, thus to clinical outcome. P53mutations are found in 14% of malignant thyroid tumors and are more frequent in poorly differentiated and anaplastic tumors. We have examined the mutation rates of p53 as a measure of genomic instability (hypermutability) ofmalignant thyroid tumors. We also wondered whether radiation enhances thistendency to genomic instability. To those ends we extracted all available entries from the p53 mutations database (http://www.perso@curies.fr). verified, extended where applicable, and supplemented that information from the original published reports. We were able to locate 100 entries. The distribution of the types of p53 aberrations in thyroid cancer was similar to those in the database as a whole. The silent mutation rate of 20%, not different from the expected 25%, is consistent with a random occurrence of these mutations. This silent mutation rate is 130 times that expected and is 7 times that of the p53 database. Moreover the distribution of p53 mutations is compatible with Poisson's distribution, which, when considered in the context of the silent mutation rates, indicates that p53 is particularly hypermutable in thyroid cancer. Epigenetic deamination of CpG dinucleotides at highly transforming DNA-contact residues is a feature of poorly differentiated tumors and thus associated with tumor progression. The rates of p53 mutations in radiation-related thyroid cancers (15.4%) are similar to those in spontaneously arising tumors, although there was a highly significant heterogeneity (p<0.0005) in the residues mutated in the two tumor sets. None of theresidues mutated in radiation-related thyroid cancer involved CpG deamination. Based on the evidence of p53 hypermutability, thyroid cancer appears to exhibit remarkable genomic instability. Spontaneous epigenetic mutationalevents are involved in tumor progression. While thyroid cancer related to radiation exposure does not increase the rates of p53 mutation, they exhibit mutation at residues not involved in p53/DNA interface. (J. Endocrinol. Invest. 24: 536-545, 2001) (C) 2001, Editrice Kurtis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/09/20 alle ore 21:55:57