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Loss of heterozygosity of CDKN2A (p16INK4a) and RB1 tumor suppressor genes and possible microsatellite instability in mismatch repair mechanism found in testicular germ cell tumors

Background. Testicular germ cell tumors (TGCTs) are the most frequent malignances in young adult men. The two main histological forms, seminomas and nonseminomas, differ biologically and clinically. pRB protein and its immediate upstream regulator p16INK4a are involved in the RB pathway which is deregulated in most TGCTs. hMSH2 and BRCA1 are genes involved in DNA mismatch repair, whose deregulation is linked with genomic instability in some tumors. The objective of this study is to evaluate the occurrence of loss of heterozygosity (LOH) of the CDKN2A (p16INK4a) and RB1 tumor suppressor genes in TGCTs and search for possible LOH and microsatellite instability (MSI) of selected genes involved in DNA mismatch repair mechanism, of which hMSH2 and BRCA1 were preliminary screened. Materials and methods. Forty TGCTs (18 seminomas and 22 nonseminomas) were analyzed by polymerase chain reaction using restriction fragment length polymorphism or nucleotide repeat polymorphism method. Results. LOH of the CDKN2A was found in two (6%) out of 34 (85%) informative cases of our total TGCT sample. The observed changes were assigned to two (11%) nonseminomas out of 18 (82%) informative samples. LOH of the RB1 was detected in two (6%) out of 34 (85%) informative cases of our total TGCT sample, and the observed changes were assigned to two (10.5%) nonseminomas out of 19 (86%) informative samples. Both LOHs of the CDKN2A were found in nonseminomas with a yolk sac tumor component, and both LOHs of the RB1 were found in nonseminomas with an embryonal carcinoma component in screening Possible MSI of both hMSH2 and BRCA1 was observed in small number of seminomas during preliminary analyses, but results still need to be validated. LOH was not observed for those genes. Conclusions. Higher incidence of observed LOH in nonseminomas may provide a clue to their invasive behavior.

testicular germ cell tumors; seminoma; nonseminoma; loss of heterozygosity; microsatellite instability; CDKN2A; RB1; hMSH2; BRCA1

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