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2009, vol. 56, iss. 4, pp. 171-175
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Mutation status of p53 gene in oral squamous cell carcinoma
Mutacioni status gena p53 u oralnim skvamocelularnim karcinomima
aUniversity of Belgrade, Faculty of Dental Medicine bUniversity of Belgrade, Faculty of Medicine, Institute of Biology and Human Genetics cUniversity of Belgrade, Faculty of Dental Medicine, Department of Maxillofacial Surgery
email: brankapo@verat.net
Project: Projekat Ministarstva nauke Republike Srbije, br. 1454042
Ključne reči: gen p53; tačkaste mutacije; oralni skvamocelularni karcinom
Abstract
Introduction. p53 gene is the most common tumor suppressor gene involved in pathogenesis oral squamous cell carcinoma (OSCC). Protein product of p53 gene contributes to cell cycle control and apoptosis. p53 gene mutations may lead to uncontrolled cell growth. The aim of this study was to determine the incidence of mutation in DNA-binding domain of p53 gene. Materials and Methods. In the 60 specimens, the presence of point mutation in exons 5, 6, 7 and 8 was detected using PCR-SSCP method. To confirm the presence of p53 mutation found by SSCP method, five samples were analyzed by sequencing of exon 5. Results. Point mutation affecting exons 5, 6, 7 and 8 were found in 60% of analyzed samples. A higher incidence of mutation was detected in exon 7 and 8 (60%), than in exon 5 and 6. Sequencing of exon 5, confirmed the presence of mutations revealed by SSCP method. Study of associations showed an increase of p53 mutations in poor differentiated and carcinoma of higher clinical stages. Conclusion. p53 gene is one of major factor in control of cell cycle and has important role in pathogenesis of oral squamous cell carcinoma.
Sažetak
Uvod. TP53 je ključni tumor-supresorski gen uključen u patogenezu oralnih skvamocelularnih karcinoma (OSCK). Proteinski proizvod gena p53 zadužen je za kontrolu ćelijskog ciklusa i apoptozu, a mutacije u TP53 mogu dovesti do nekontrolisane proliferacije ćelija. Cilj ovog rada je bio da se utvrdi zastupljenost tačkastih mutacija u regionu gena p53 koji se vezuje za DNK, odnosno proceni uloga ovoga gena u patogenezi OSCK. Materijal i metode rada. U 60 uzoraka OSCK su korišćenjem metode lančane reakcije polimeraze i polimorfizma jednolančanih fragmenata DNK (PCR-SSCP) ispitane tačkaste mutacije u egzonima 5, 6, 7 i 8 gena p53. Pet slučajno odabranih uzoraka u kojima je otkrivena mutacija naknadno je podvrgnuto sekvenciranju radi potvrde validnosti metode PCR-SSCP. Rezultati. Tačkaste mutacije u nekom od analiziranih egzona gena p53 utvrđene su u 60% uzoraka OSCK. Veća učestalost mutacija zabeležena je u egzonima 7 i 8. Sekvenciranje je potvrdilo mutacije otkrivene metodom SSCP. Studija asocijacije pokazuje povećanje broja mutacija gena p53 kod slabo diferenciranih i karcinoma viših kliničkih stadijuma. Zaključak. Gen p53, jedan od glavnih kontrolora ćelijskog ciklusa, ima značajnu ulogu i u patogenezi karcinoma oralne duplje.
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