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2013, vol. 32, br. 4, str. 380-388
Simultana alteracija TP53 i c-myc gena - obeležje progresije oralnih karcinoma
aUniverzitet u Beogradu, Institut za nuklearne nauke Vinča, Beograd-Vinča
bUniverzitet u Beogradu, Stomatološki fakultet
cUniverzitet u Beogradu, Stomatološki fakultet, Klinika za maksilofacijalnu hirurgiju
dUniverzitet u Beogradu, Institut za biološka istraživanja 'Siniša Stanković'

e-adresanastad@vinca.rs
Projekat:
Identifikacija molekularnih markera za predikciju progresije tumora, odgovora na terapiju i ishoda bolesti (MPNTR - 41031)
Molekularne determinante za dizajn tumor markera (MPNTR - 173049)

Ključne reči: c-myc; onkogeni; progresija tumora; TP53; tumor supresori; skvamocelularni karcinom usne duplje
Sažetak
Uvod: Skvamocelularni karcinomi glave i vrata (HNSCC) uključujući i skvamocelularni karcinom usne duplje (OSCC) ubrajaju se u šest najčešćih tipova humanih maligniteta. Uprkos značajnim napredcima u hirurškom i terapijskom tretmanu, stopa petogodišnjeg preživljavanja kod ovog tipa maligniteta nije značajnije popravljena. Upravo zato, definisanje pouzdanih molekularnih markera progresije kod OSSC predstavlja apsolutni prioritetet. Metode: Amplifikacioni status c-myc, cycD1 i EGFR gena određen je pomoću eseja za detekciju broja genskih kopija, aktivacija H-ras onkogena i inaktivacija TP53 tumor supresora određena je PCR-SSCP mutacionom analizom, a hipermetilacija promotora p16 i MGMT gena je ispitana metil specifičnim PCR-om (MSP). Rezultati: Amplifikacija c-myc onkogena detektovana je kod 56,7%, cycD1 onkogena kod 20%, a EGFR onkogena kod 16,7% analiziranih oralnih skvamocelularnih carcinoma. Istovremeno, mutaciona aktivacija H-ras onkogena detektovana je kod 33,3% ispitanih uzoraka. Amplifikovani c-myc, statistički značajno korelira sa gradusom 2 OSCC. Posebno intrigantan je bio nalaz po kom se onkogene aktivacije u EGFR i H-ras genu međusobno isključuju. Hipermetilacija promotora p16 gena detektovana je kod 30%, a MGMT kod 13,3% analiziranih uzoraka. Ko-alteracije cycDI i p16 gena nisu zapažene ni u jednom od analiziranih uzoraka. Inaktivacija TP53 gena detektovana je kod 56,7% uzoraka i utvrđeno je da statistički značajno korelira sa gradusom 2 i statusom 2 OSCC. Pored ovoga, utvrđeno je da statistički značajan broj uzoraka gradusa 2, sa aktiviranim TP53 genom ima istovremeno aktiviran i c-myc onkogen. Zaključak: TP53, najčešće mutirani gen u oralnim karcinomima, ostaje za sada i najpouzdaniji marker progresije kod OSCC. Obzirom na detektovani sinergizam između TP53 i c-myc gena, možemo reći da su istovremene promene u ova dva gena još pouzdaniji pokazatelj progresije OSSC iz gradusa 1 u gradus 2.
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O članku

jezik rada: engleski
vrsta rada: izvorni članak
DOI: 10.2478/jomb-2014-0009
objavljen u SCIndeksu: 13.11.2013.

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