engleski

ALTERATIONS OF SELECTED GENES IN TESTICULAR GERM CELL TUMORS: CAN THEY HELP PREDICT CLINICAL OUTCOME?

Human testicular germ cell tumors (TGCTs) are histologically heterogenous neoplasms with common origin and variable malignant potential. Two main groups, seminomas and nonseminomas, differ biologically and clinically. Embryonal carcinoma component of nonseminoma is proved so far to be the most relevant for clinical tumor prognosis, based on histology. In the present study a set of genes involved in cell adhesion (CDH1, APC, nm23-H1), cell cycle regulation (CDKN2A, RB1, TP53), DNA damage repair (BRCA1, hMLH1, hMSH2, hRAD51), apoptosis regulation (BAX) and multidrug resistance phenotype (ABCG2) was investigated in forty TGCTs to evaluate the occurrence of loss of heterozygosity (LOH) and microsatellite instability (MSI). Both provide information about whole genome integrity and structural changes of particular key genes. Different pattern of LOH has been shown between the two TGCTs groups, suggesting of independent development. Incidence of LOH in embryonal carcinoma was only moderately elevated. LOHs of several genes with synergistic effect (CDH1, CDKN2A, RB1, TP53), as well as higher incidence of LOH in TGCTs harboring highly metastatic and chemoresistant histological components, may provide a clue to their invasive behavior. No MSI has been observed, implying no structural damage to the genes responsible for DNA damage repair. This is in agreement with the fact that most of TGCTs respond well to therapy.

seminoma; nonseminoma; loss of heterozygosity; microsatellite instability

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