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Characteristic promoter hypermethylation signatures in male germ cell tumors

Authors
  • Koul, Sanjay1
  • Houldsworth, Jane2
  • Mansukhani, Mahesh M1
  • Donadio, Alessia3
  • McKiernan, James M4
  • Reuter, Victor E5
  • Bosl, George J3
  • Chaganti, Raju S3
  • Murty, Vundavalli V1, 6
  • 1 Surgeons of Columbia University, Department of Pathology, College of Physicians &, 630 West 168th Street, New York, NY, 10032, USA , New York
  • 2 Memorial Sloan-Kettering Cancer Center, Cell Biology Program, 1275 York Avenue, New York, NY, 10021, USA , New York
  • 3 Memorial Sloan-Kettering Cancer Center, Department of Medicine, 1275 York Avenue, New York, NY, 10021, USA , New York
  • 4 Surgeons of Columbia University, Department of Urology, College of Physicians &, 630 West 168th Street, New York, NY, 10032, USA , New York
  • 5 Memorial Sloan-Kettering Cancer Center, Department of Pathology, 1275 York Avenue, New York, NY, 10021, USA , New York
  • 6 College of Physicians & Surgeons of Columbia University, Institute for Cancer Genetics, 630 West 168th Street, New York, NY, 10032, USA , New York
Type
Published Article
Journal
Molecular Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 28, 2002
Volume
1
Issue
1
Identifiers
DOI: 10.1186/1476-4598-1-8
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundHuman 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.ResultsTo 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.ConclusionsOur results, therefore, suggest a potential role for epigenetic modification of critical tumor suppressor genes in pathways relevant to GC transformation, differentiation, and treatment response.

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