Characteristic promoter hypermethylation signatures in male germ cell tumors. Academic Article uri icon

Overview

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 pluripotentiality 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 occurred 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.

publication date

  • November 28, 2002

Research

keywords

  • Azacitidine
  • DNA Methylation
  • Gene Expression Regulation, Neoplastic
  • Neoplasms, Germ Cell and Embryonal
  • Promoter Regions, Genetic

Identity

PubMed Central ID

  • PMC149411

Scopus Document Identifier

  • 0344081258

Digital Object Identifier (DOI)

  • 10.1093/jnci/92.7.564

PubMed ID

  • 12495446

Additional Document Info

volume

  • 1