Year: 2006
Type: dissertation
Study design: Observational Study
Abstract: Human germ cell tumours (GCTs) can be classified into five distinct types, based on differences in anatomical location, histology, clinical outcome, age and genotype. The first type, the type I GCTs primarily occur in neonates and infants under the age of five years and include teratomas and yolk sac tumours with distinct clinical and epidemiologic features. As yet, little is known about the (cyto)genetic constitution of these tumours. The objectives of this thesis were to identify (i) candidate genes involved in the development of type I GCTs and (ii) chromosomal anomalies that may serve as diagnostic/prognostic markers for these tumours. To these ends, we positionally cloned two constitutional chromosome translocations in patients with type I GCTs and breakpoints in the 12q11-q13 region, a region thought to harbour gene(s) involved in GCT development. The constitutional t(12;15)(q13;q25) translocation gave rise to reciprocal fusion genes, revealing two candidate genes for type I GCT development: MESDC2 and SENP1. In addition, a series of sporadic type I GCTs were analysed for recurrent chromosomal anomalies using array CGH. Three subgroups could be distinguished by their genomic profiles: 1) teratomas of patients (<5 years) displaying normal profiles, except for some minor recurrent aberrations, 2) yolk sac tumours of patients (<5 years) displaying recurrent losses of 1p35-pter and gains of 3p21-pter and of 20q13 and 3) GCTs of patients (> 5 years) displaying recurrent gains of 12p, chromosomes 7 and 8. Independent of age and histology, gains of the 1q32-qter region and losses of the 6q24-qter and 18q21-qter regions were frequent events in these GCTs. From these results we conclude that array-based genomic profiles may be used as diagnostic/prognostic identifiers for type I GCTs and the recurrent anomalies may point at chromosomal regions that harbour genes relevant for the development of these neoplasms.
Author: Imke M. Veltman
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Deutsche Krebshilfe
OpenAlex ID: W1604653249