GENETIČKE PROMENE U MELANOMU

Marija Dunjić; Dijana Perović; Gordana Šupić

doi:10.5937/mp76-48374

Marija Dunjić Medicinski fakultet Univerziteta u Beogradu
Dijana Perović Institut za humanu genetiku, Medicinski fakultet Univerziteta u Beogradu
Gordana Šupić Medicinski fakultet VMA Univerziteta odbrane u Beogradu, Institut za Medicinska istraživanja VMA u Beogradu

DOI: https://doi.org/10.5937/mp76-48374

Ključne reči: melanom, genetika, signalni putevi

Sažetak

Melanom, agresivni maligni tumor kože s visokom stopom smrtnosti u uznapredovalim stadijumima, predstavlja globalni zdravstveni izazov. Genetičke promene igraju ključnu ulogu u razvoju i progresiji ove bolesti.

Prethodnih godina pokazana je povezanost melanoma s promenama u signalnim putevima koji učestvuju u regulaciji ćelijskog ciklusa. Najznačajnija povezanost ovog tipa je sa MAPK signalnim putem, a prema dosadašnjim studijama u preko 80% melanoma uočene su mutacije u genima BRAF, RAS i NF1, koji su ključni članovi ovog signalnog lanca. U skladu s tim razvijena je ciljana terapija poput BRAF i MEK inhibitora. Međutim, česta sekundarna rezistencija na ovu terapiju kao i postojanje melanoma bez ovih mutacija, poznatih kao "trostruki divlji tip",naglašava potrebu za daljim genetičkim istraživanjima i unapređenjem terapijskih strategija.

Mutacije u genima poput KIT, GNAQ/11, PTEN i TERT takođe su povezane sa patogenezom melanoma, a neke od njih i s određenim podtipovima ovog tumora. Nasledna predispozicija je prisutna u svega 5-10% slučajeva, a kao dva najčešća gena familijarne forme melanoma identifikovani su CDKN2A i CDK4.

Kao glavni faktor rizika za formiranje specifičnog genetičkog profila melanoma pokazala se izloženost UV zračenju sa nastankom ,,mutacija UV potpisa"koje dalje dovode do grešaka pri replikaciji DNK i melanomageneze. Sem toga, mutacije i varijacije u genima koji prilikom sunčanja regulišu sintezu zaštitnog pigmenta eumelanina, kao što su MC1R i MITF, predstavljaju faktor rizika za razvoj ove bolesti.

Proučavanje prekursorskih lezija, uključujući melanocitne nevuse, doprinilo je razumevanju genetičke evolucije melanoma. Identifikacija mutacija poput BRAF V600E u ovim lezijama ističe ulogu dodatnih genetičkih promena u malignoj transformaciji.

Od budućih istraživanja očekuje se identifikacija novih genetičkih markera koji bi unapredili razumevanje, prevenciju i dijagnostiku melanoma, što će omogućiti personalizovani pristup lečenju u cilju poboljšanja efikasnosti i smanjenja neželjenih efekata terapije.

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