engleski

GENETIC BACKGROUND OF TESTICULAR GERM CELL TUMORS: FROM CHEMOSENSITIVITY TO CHEMORESISTANCE?

Human testicular germ cell tumors (TGCTs) are histologically heterogenous neoplasms with variable malignant potential. Two main groups, seminomas and nonseminomas, differ biologically and clinically. Considered to have a common origin, little is known about their development and cellular mechanisms involved in response to therapy. In order to gain insight about the role of genetic background in development and clinical outcome of TGCTs, 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) was investigated in forty TGCTs. In TGCT tissue samples, occurrence of loss of heterozygosity (LOH) and microsatellite instability (MSI) was evaluated. Those genetic alterations provide information about whole genome integrity, as well as structural changes in particular key genes. Different pattern of LOH has been observed between the two TGCTs groups and no common structural genetic alteration was found, indicative 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.

seminomas ; nonseminomas ; loss of heterozygosity ; microsatellite instability

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