Več obrazov sindroma Lynch Multiple faces of the Lynch syndrome

detection of germ-line mutations in the MSH6 gene

Abstract

Na Oddelku za molekularno diagnostiko Onkološkega inštituta Ljubljana smo uvedli testiranje zarodnih mutacij vgenu MSH6. Mutacije v tem genu so povezane z Lynchevim sindromom in predstavljajo povečano verjetnost za nastanekraka na debelem črevesu in danki, raka maternične sluznice,raka jajčnikov in drugih vrst raka. Za testiranje prisotnosti mutacij v genu MSH6 uporabljamo metodo neposrednega sekvenciranja in metodo MLPA (ang. multiplex ligation-dependentprobe 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. Mutacije v genu MSH6 testiramo pri osebah, za katere se v postopku genetskega svetovanja pokaže večja verjetnost Lynchevega sindroma. Pravočasno odkrivanje mutacij v genih, povezanih z nastankom raka, je za nosilce mutacij pomembno, saj je dokazana mutacija razlog za prilagojeno klinično spremljanje in preventivne ukrepe pri nosilcih mutacije. ; slv - slovenski

Abstract (Eng)

The Department of Molecular Diagnostics at the Institute of Oncology Ljubljana has introduced testing of germ-line mutations in the MSH6 gene. Mutations in this gene are associated with the Lynch syndrome and represent an increased likelihood for the development of colorectal, endometrial, ovarian, and other cancers. The presence of mutations in the MSH6 gene 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. Mutations in the MSH6 gene are tested in persons who, in the process of genetic counselling, show an increased likelihood of developing Lynch syndrome. A timely detection of mutations in the genes associated with the development of cancer is important for the carriers of mutations, as a proven mutation is a reason for individualised clinical monitoring and/or preventive measures in mutation carriers.