Določanje mutacij pri bolnikih z dedno obliko malignega melanoma kože Screening for melanoma susceptibility gene mutations in patients with familial cutaneous melanoma

Abstract

Gensko testiranje za dedno obliko malignega melanoma kože na OI Ljubljana opravljamo od leta 2005. Izbor bolnikov za testiranje poteka v okviru genetskega svetovanja. Testiramo bolnike in njihove zdrave sorodnike, če sta v družini najmanj dva obolela člana, in bolnike s primarnimi multiplimi melanomi brez obremenjujoče družinske anamneze. Na oddelku za molekularno diagnostiko z metodo sekvenčne analize iščemo in določamo neznane točkovne mutacije ter manjše delecije in insercije v eksonih genov, povezanih z nastankom malignega melanoma kože: CDKN2A, CDK4 in MC1R. Do sedaj smo testirali 70 oseb: 40 bolnikov in njihovih zdravih sorodnikov iz 28 različnih družin, obremenjenih z družinsko anamnezo, ter 30 bolnikov s primarnimi multiplimi melanomi. Sekvenčna analiza genov, povezanih z dedno obliko malignega melanoma kože, je pokazala, da so mutacije CDKN2A p16INK4a pri bolnikih z družinsko anamnezo zelo pogoste (37,5 %). Mutacij CDKN2A p14ARF in CDK4 pri slovenskih bolnikih nismo našli.

Abstract (Eng)

At the Institute of Oncology Ljubljana, Department of Molecular Diagnostics, genetic testing for familial cutaneous melanoma (CM) was started in 2005. The patients are selected according to the guidelines of genetic counseling for CM. The screening for melanoma susceptibility genes is performed in the patients and their healthy relatives from the families with at least two affected family members and in the patients with multiple primary CM without family history. The mutation screening for melanoma susceptibility genes – CDKN2A, CDK4 and MC1R is performed by direct sequencing. Altogether 70 patients and their healthy relatives (40 patients or their relatives selected from 28 families after considering their on family history and 30 patients with multiple primary CM) have been tested so far. Our results showed high prevalence of CDKN2A p16INK4a mutations in the patients with familial CM. In CDKN2A p14ARF and CDK4, no mutations were detected in Slovenian patients.