Development Of Testicular Germ Cell Tumors Research Articles

An excess of testicular germ cell tumors in down's syndrome

BACKGROUND The incidence of specific solid tumors in Down's syndrome (DS) is not well established. Testicular germ cell tumors (TGCT) might be increased in this population. METHODS The presence of TGCT among male subjects from the French department of Corrèze was recorded and literature on the subject reviewed. RESULTS A total of 120 living children and adults with DS and 17 pregnancies (12 births and 5 therapeutic abortions) were examined over an 8-year period (1987-1994). Three TGCT were diagnosed. A seminoma and an embryonal carcinoma were observed in two young adults and an intratubular germ cell neoplasm in a 22-week-old fetus. Because testicular tumors occur at an incidence rate of 4 cases per 100,000 person-years in the general population, these observations suggest a clearly increased risk of developing TGCT in the DS population. In addition, a review of the literature also shows an excess of TGCT in this population. Cryptorchidism alone, which is prevalent in individuals with DS, cannot explain this significantly increased incidence of TCGT. The authors hypothesize that an excess of luteinizing hormone and follicle-stimulating hormone gonadotropins and overexpression of the Ets-2 gene through gene dosage effect could predispose patients with DS to the development of TGCT. CONCLUSIONS Surveillance of the gonads of male patients with DS is recommended. A better understanding of the factors involved could also help to identify risk factors in the general population. Cancer 1997; 80:929-35. © 1997 American Cancer Society.

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.