Molecular cytogenetics of human germ cell tumours: i(12p) and related chromosomal anomalies.
Human testicular germ cell tumours (TGCTs) comprise a heterogeneous group of solid neoplasms. These tumours are characterized by a highly specific chromosomal anomaly, i.e. an isochromosome of the short arm of chromosome 12. At present, this i(12p) chromosome has been observed in about 80% of TGCTs. Also in dysgerminomas of the ovary and in some extragonadal germ cell tumours i(12p) has been observed. In the remaining so-called i(12p)-negative tumours other cytogenetic abnormalities can be found. In addition, TGCTs are usually highly aneuploid. The exact nature and role of these different anomalies in tumour development are as yet undefined. Here we present a molecular cytogenetic analysis of a diverse group of gonadal and extragonadal germ cell tumours. Our results indicate that all tumours examined exhibit anomalies involving 12p [i(12p) and/or others], resulting in a distinct overrepresentation of short arm sequences. Thus, we argue that the occurrence of 12p abnormalities may be a characteristic of both i(12p)-positive and -negative TGCTs and that these abnormalities may, through similar mechanisms, contribute to the process of TGCT development. This notion is substantiated by our finding that in all cases the supernumerary 12p sequences are of uniparental origin.
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