Allelic losses in carcinoma in situ and testicular germ cell tumours of adolescents and adults: evidence suggestive of the linear progression model

摘要: Testicular germ cell tumours (TGCTs) may arise through a process of multi-step carcinogenesis, and loss heterozygosity (LOH) at specific loci is likely to be an important early event, although this has not been studied in detail. In order explore the pathogenetic relationships among TGCTs, we investigated genetic changes testicular that exhibit disease continuum precursor carcinoma situ (CIS) either seminoma (SE) and/or non-seminomatous tumour (NSGCT). Universal amplification performed on 87 TGCT specimens 36 samples CIS cells microdissected from single paraffin-embedded sections 40 patients, including multiple varied histology 24 individual patients. Seventy-seven microsatellite markers were used assay these for LOH candidate regions selected literature, mapping 3q, 5q, 9p, 11p, 11q, 12q, 17p 18q. Construction deletion maps each identified common sites 3q27–q28, 5q31, 5q34–q35, 9p22–p21 12q22, which correlate with allelic losses have also observed cells. Evidence 3q27–q28 was all embryonal analysed. We conclude inactivation gene(s) within are events development progression TGCTs. These results provide molecular evidence support hypothesis SE intermediate stage neoplastic pathway NSGCT. © 2000 Cancer Research Campaign