Characteristic promoter hypermethylation signatures in male germ cell tumors Journal Article
| Authors: | Koul, S.; Houldsworth, J.; Mansukhani, M.; Donadio, A.; McKiernan, J. M.; Reuter, V. E.; Bosl, G. J.; Chaganti, R. S.; Murty, V. V. |
| Article Title: | Characteristic promoter hypermethylation signatures in male germ cell tumors |
| 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. © 2002 Koul et al; licensee BioMed Central Ltd. |
| Keywords: | controlled study; human tissue; human cell; promoter region; genetics; histopathology; cisplatin; polymerase chain reaction; neoplasm; metabolism; dna repair; gene expression; molecular dynamics; transcription factor; cell differentiation; drug effect; pathology; cell line, tumor; brca1 protein; dna methylation; gene expression regulation; tumor suppressor gene; gene activation; gene expression regulation, neoplastic; dna modification; transcription regulation; messenger rna; rna, messenger; epigenetics; cell transformation; cpg island; cpg islands; epigenesis, genetic; promoter regions, genetic; tumor cell line; drug response; drug derivative; 5 aza 2' deoxycytidine; ras protein; neoplasms, germ cell and embryonal; gene silencing; methylated dna protein cysteine methyltransferase; germ cell tumor; repressor protein; repressor proteins; drug sensitivity; genetic epigenesis; brca1; seminoma; genes, tumor suppressor; azacitidine; non seminomatous germinoma; complementary dna; mgmt; promoter hypermethylation; rassf1a; humans; human; male; article; primordial germ cell |
| Journal Title: | Molecular Cancer |
| Volume: | 1 |
| ISSN: | 1476-4598 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2002-11-28 |
| Start Page: | 8 |
| Language: | English |
| DOI: | 10.1186/1476-4598-1-8 |
| PUBMED: | 12495446 |
| PROVIDER: | scopus |
| PMCID: | PMC149411 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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