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Molecular Cancer
Published in: Molecular Cancer 1/2002

Open Access 01-12-2002 | Research

Characteristic promoter hypermethylation signatures in male germ cell tumors

Authors: Sanjay Koul, Jane Houldsworth, Mahesh M Mansukhani, Alessia Donadio, James M McKiernan, Victor E Reuter, George J Bosl, Raju S Chaganti, Vundavalli V Murty

Published in: Molecular Cancer | Issue 1/2002

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Abstract

Background

Human male germ cell tumors (GCTs) arise from undifferentiated primordial germ cells (PGCs), a stage in which extensive methylation reprogramming occurs. GCTs exhibit pluripotentality and are highly sensitive to cisplatin therapy. The molecular basis of germ cell (GC) transformation, differentiation, and exquisite treatment response is poorly understood.

Results

To assess the role and mechanism of promoter hypermethylation, we analyzed CpG islands of 21 gene promoters by methylation-specific PCR in seminomatous (SGCT) and nonseminomatous (NSGCT) GCTs. We found 60% of the NSGCTs demonstrating methylation in one or more gene promoters whereas SGCTs showed a near-absence of methylation, therefore identifying distinct methylation patterns in the two major histologies of GCT. DNA repair genes MGMT, RASSF1A, and BRCA1, and a transcriptional repressor gene HIC1, were frequently methylated in the NSGCTs. The promoter hypermethylation was associated with gene silencing in most methylated genes, and reactivation of gene expression occured upon treatment with 5-Aza-2' deoxycytidine in GCT cell lines.

Conclusions

Our results, therefore, suggest a potential role for epigenetic modification of critical tumor suppressor genes in pathways relevant to GC transformation, differentiation, and treatment response.
Appendix
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Metadata
Title
Characteristic promoter hypermethylation signatures in male germ cell tumors
Authors
Sanjay Koul
Jane Houldsworth
Mahesh M Mansukhani
Alessia Donadio
James M McKiernan
Victor E Reuter
George J Bosl
Raju S Chaganti
Vundavalli V Murty
Publication date
01-12-2002
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2002
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-1-8

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