A physical analysis of the Y chromosome shows no additional deletions, other than Gr/Gr, associated with testicular germ cell tumour

Testicular germ cell tumour (TGCT) is the most common malignancy in men aged 15–45 years. A small deletion on the Y chromosome known as ‘gr/gr' was shown to be associated with a two-fold increased risk of TGCT, increasing to three-fold in cases with a family history of TGCT. Additional deletions of the Y chromosome, known as AZFa, AZFb and AZFc, are described in patients with infertility; however, complete deletions of these regions have not been identified in TGCT patients. We screened the Y chromosome in a series of TGCT cases to evaluate if additional deletions of Y were implicated in TGCT susceptibility. Single copy Y chromosome STS markers with an average inter-marker spacing of 128 kb were examined in constitutional DNA of 271 index TGCT patients. Three markers showed evidence of deletions, sY1291, indicative of ‘gr/gr' (eight out of 271; 2.9%), Y-DAZ3 contained within ‘gr/gr' (21 out of 271; 7.7%) and a single deletion of the marker G66152 was identified in one TGCT case. No other markers demonstrated deletions. While several regions of the Y chromosome are known to be deleted and associated with infertility, our study provides no evidence to suggest regions of Y deletion, other than ‘gr/gr', are associated with susceptibility to TGCT in UK patients

Genetic predisposition to testicular germ-cell tumours

Testicular germ-cell tumours (TGCT) are the most common neoplasm in young men. Various studies have suggested the existence of an inherited predisposition to development of these tumours. Genome-wide screens subsequently provided evidence of a TGCT susceptibility gene on chromosome Xq27 (TGCT1) that might also predispose to cryptorchism. However, this putative gene has yet to be identified, and other TGCT susceptibility genes probably exist. Completion of the human gene map and advances in genetic research will facilitate further investigation of genetic predisposition to TGCT. Insight into inheritance of TGCT might lead to the identification of individuals at increased risk of developing the disorder, increase our understanding of the mutation pathways that lead to sporadic cases, and contribute to improvement in diagnosis and treatment. Clinicians should record the family history of cancer and urogenital differentiation defects in patients with TGCT

Non-germ cell malignancy in residual or recurrent mass after chemotherapy for nonseminomatous testicular germ cell tumor

Background: After chemotherapy for nonseminomatous testicular germ cell tumor (NSTGCT), residual masses or recurrent disease may contain a non-germ cell malignancy (NGCM). Methods: Over 20 years, 369 patients with disseminated NSTGCT were treated with cisplatin-based polychemotherapy at the University Medical Center Groningen. Residual tumor masses were resected in 244 patients and recurrent tumor masses in 37 patients. Histology was reviewed, focusing on the presence of NGCM. Results: Nine patients developed an NGCM. Four patients had an NGCM in the resected residual tumor mass after chemotherapy: three patients had a sarcoma, and one patient had both a sarcoma and an adenocarcinoma. Five patients developed a late recurrence with an NGCM after 39, 40, 72, 72, and 84 months. One patient had a primitive neuroectodermal tumor, one had a sarcoma, and three had an adenocarcinoma in the resected recurrent tumor mass. A complete surgical resection was achieved in five (56%) of the nine patients. After a median follow-up of 48 months (range, 3-271 months), five patients had no evidence of disease (56%), three patients were dead of disease (33%), and one patient was alive with disease (11%). Conclusions: Sarcoma, adenocarcinoma, or both in residual or recurrent tumor masses after combined-modality NSTGCT treatment are rare. Complete surgical resection of the tumor mass is the only curative treatment option

Absence of constitutional Y chromosome AZF deletions in patients with testicular germ cell tumors

Objectives. To investigate the frequency of azoospermia factor (AZF) deletions in Dutch patients with testicular germ cell tumors (TGCTs). Reduced fertility is associated with TGCTs and reduced fertility and TGCTs might share genetic risk factors according to the testicular dysgenesis hypothesis. Up to 8% of infertility and reduced fertility in the general male population can be explained by the presence of constitutional deletions of part of the long arm of the Y chromosome (Yq11), referred to as the AZF region. Methods. In 112 patients with TGCT, screening for constitutional deletions in the AZF region was performed by multiplex polymerase chain reaction analysis in DNA extracted from peripheral blood lymphocytes. A set of 24 primer pairs, of which 20 primer pairs are homologous to previously identified and mapped sequenced tag sites within the AZF region were used. Results. No deletions in the Yq11 region were detected in any of the 112 patients. Conclusions. Large Y chromosome microdeletions in the AZF region are not a major contributor to the development of TGCT and TGCT-associated reduced fertility. (C) 2005 Elsevier Inc

Testicular carcinoma and HLA class II genes

BACKGROUND. The association with histocompatibility antigens (HLA), in particular Class II genes (DQB1, DRB1), has recently been suggested to be one of the genetic factors involved in testicular germ cell tumor (TGCT) development. The current study, which uses genotyping of microsatellite markers, was designed to replicate previous associations. METHODS. In 151 patients, along with controls comprising parents or spouses, the HLA region (particularly Class II) on chromosome 6p21 was genotyped for a set of 15 closely linked microsatellite markers. RESULTS. In both patients and controls, strong linkage disequilibrium was observed in the genotyped region, indicating that similar haplotypes are likely to be identical by descent. However, association analysis and the transmission disequilibrium test did not show significant results. Haplotype sharing statistics, a haplotype method that derives extra information from phase and single marker tests, did not show differences in haplotype sharing between patients and controls. CONCLUSION. The current genotyping study did not confirm the previously reported association between HLA Class II genes and TGCT. As the HLA alleles for which associations were reported are also prevalent in the Dutch populations, these associations are likely to be nonexistent or much weaker than previously reported