Elsevier

Urology

Volume 65, Issue 1, January 2005, Pages 196-201
Urology

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

https://doi.org/10.1016/j.urology.2004.09.022Get rights and content

Abstract

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.

Section snippets

Patient selection

A total of 112 patients with TGCT treated at the Groningen University Medical Center (GUMC) in The Netherlands were randomly selected for initial analysis. Patient characteristics are listed in Table I. Familial TGCT was defined as more than 1 case in the family. Histologic diagnosis was established in all patients by the Department of Pathology of the GUMC. Owing to the position of our medical center (academic referral hospital for the northern part of The Netherlands), most patients had

Results

Microdeletions analysis of the AZF region (Yq11) was successfully performed on genomic DNA of 112 patients with TGCT. Figure 2 includes representative examples of the electrophoresis gels, showing amplification products for multiplex A-E. No PCR products were detected in the blank (no DNA) control. As expected, the positive male control showed the appropriate number and sizes of bands for each multiplex master mix. The positive female control only showed amplification for the SMCX and ZFX loci.

Comment

A detailed analysis of microdeletions on the Y chromosome was performed in 112 Dutch patients with TGCT by studying 24 STSs within the AZF regions on Yq11. These patients included bilateral cases (n = 4), cases with cryptorchism (n = 21), cases with a positive family history (n = 10) for TGCT (Table I), and patients with proven normal or low sperm counts (Table II). No AZF deletions were observed in any of the patients. The distribution of nonseminomatous TGCTs and seminomatous TGCTs (Table I)

Conclusions

The data suggest that a substantial contribution of constitutional large AZF deletions to the development of TGCT, whether or not in the presence of reduced fertility, cryptorchism, previous history of TGCT, or positive family history, is unlikely. The present data do not rule out the possibility of constitutional smaller deletions or other type of mutations in genes mapped to the AZF region. These genes could, therefore, be the subject of additional research. Given the complexity of urogenital

Acknowledgment

To Jan Osinga for technical support in the AZF analysis.

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This work was supported by a grant from the “Jan Kornelis de Cock” Foundation.

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