Odkrivanje dednega sindroma von Hippel-Lindau Detection of the von Hippel-Lindau hereditary cancer syndrome

determination of mutations in the VHL gene

Abstract

Na Oddelku za molekularno diagnostiko Onkološkega inštituta Ljubljana smo uvedli testiranje mutacij v tumorskem supresorskem genu von Hippel-Lindau (VHL). Mutacije v tem genu povečajo verjetnost za nastanek rakastih bolezni, povezanih s sindromom »von Hippel-Lindau« (VHL), kakor tudi z nastankom sporadičnega raka ledvic. Testiranje dednih mutacij pri bolnikih s sumom na sindrom VHL omogoča zgodnjo pravilno diagnozo bolezni. Prisotnost mutacije v genu VHL je dovolj za potrditev diagnoze sindroma VHL tudi ob odsotnosti značilnih tumorjev. Za testiranje prisotnosti mutacij v genu VHL uporabljamo metodo neposrednega sekvenciranja in metodo MLPA (ang. multiplex ligation-dependent probe amplification). S sekvenciranjem odkrivamo točkovne mutacije in manjše delecije ter insercije. Z metodo MLPA pa prisotnost večjih delecij in insercij v genu oziroma delecijo celotnega gena. Pravočasno odkrivanje mutacij v genih, povezanih z nastankom raka, je za nosilce mutacij pomembno, saj je dokazana mutacija razlog za prilagojeno klinično spremljanje in/ali preventivne ukrepe pri nosilcih mutacije. Posledično so zaradi tega povečane možnosti za preprečevanje ali zgodnejše odkrivanje raka.

Abstract (Eng)

The Department of Molecular Diagnostics at the Institute of Oncology Ljubljana has introduced testing of mutations in the von Hippel-Lindau (VHL) suppressor gene. Mutations in this gene increase the probability for the development of cancerous diseases associated with the »von Hippel-Lindau« (VHL) syndrome and also the development of sporadic kidney cancer. Testing of hereditary mutations in patients suspected of having the VHL syndrome enables early and correct diagnosis of the disease. Presence of a mutation in the VHL gene is sufficient to confirm the diagnosis of VHL syndrome also in the absence of typical tumours. It is tested using the direct sequencing method and the MLPA multiplex ligation-dependent probe amplification) method. While sequencing allows us to detect point mutations and small deletions and insertions, the MLPA method is used to detect the presence of large deletions and insertions in the gene or a deletion of the entire gene. Timely detection of mutations in genes associated with the development of cancer is important for the carriers of mutations, as a proven mutation is a reason for an adapted clinical monitoring and/or preventive measures in mutation carriers. This results in increased possibilities for the prevention and early detection of cancer.