engleski

GENETIC BACKGROUND OF TESTICULAR GERM CELL TUMORS: MODERN INSIGHT AND STANDARD TREATMENT

Human testicular germ cell tumors (TGCTs) are histologically heterogenous neoplasms with variable malignant potential. Two main groups, seminomas and nonseminomas, differ biologically and clinically. Although found together in a patient, their development and evolution of clinical response is not fully understood. Despite high curability, cases of chemoresistance arise. To gain insight about the role of genetic background in development and clinical outcome of TGCTs, tissue samples were analysed for loss of heterozygosity (LOH) and microsatellite instability (MSI) within a set of genes involved in cell adhesion (CDH1, APC, NME1), cell cycle regulation(CDKN2A, RB1, TP53), DNA damage repair (BRCA1, MLH1, MSH2, RAD51), apoptosis regulation (BAX) and multidrug resistance (ABCG2). Different pattern of LOH has been observed between the two TGCTs groups and no common structural genetic alteration was found, suggesting of independent development for TGCT groups. 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 clinical behavior. The analysis of genes involved in DNA damage repair showed no changes in agreement with the fact MSI has not been observed, and most of TGCTs respond well to therapy. Genetic background of these tumors may help to develop better patient management strategies in regard to usual invasive therapy regimes.

testicular germ cell tumors; seminoma; nonseminoma; loss of heterozygosity; microsatellite instability

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