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Characteristic promoter hypermethylation signatures in male germ cell tumors
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, dif...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2002
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149411/ https://www.ncbi.nlm.nih.gov/pubmed/12495446 http://dx.doi.org/10.1186/1476-4598-1-8 |
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author | Koul, Sanjay Houldsworth, Jane Mansukhani, Mahesh M Donadio, Alessia McKiernan, James M Reuter, Victor E Bosl, George J Chaganti, Raju S Murty, Vundavalli V |
author_facet | Koul, Sanjay Houldsworth, Jane Mansukhani, Mahesh M Donadio, Alessia McKiernan, James M Reuter, Victor E Bosl, George J Chaganti, Raju S Murty, Vundavalli V |
author_sort | Koul, Sanjay |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-149411 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-1494112003-02-25 Characteristic promoter hypermethylation signatures in male germ cell tumors Koul, Sanjay Houldsworth, Jane Mansukhani, Mahesh M Donadio, Alessia McKiernan, James M Reuter, Victor E Bosl, George J Chaganti, Raju S Murty, Vundavalli V Mol Cancer Research 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. BioMed Central 2002-11-28 /pmc/articles/PMC149411/ /pubmed/12495446 http://dx.doi.org/10.1186/1476-4598-1-8 Text en Copyright © 2002 Koul et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
spellingShingle | Research Koul, Sanjay Houldsworth, Jane Mansukhani, Mahesh M Donadio, Alessia McKiernan, James M Reuter, Victor E Bosl, George J Chaganti, Raju S Murty, Vundavalli V Characteristic promoter hypermethylation signatures in male germ cell tumors |
title | Characteristic promoter hypermethylation signatures in male germ cell tumors |
title_full | Characteristic promoter hypermethylation signatures in male germ cell tumors |
title_fullStr | Characteristic promoter hypermethylation signatures in male germ cell tumors |
title_full_unstemmed | Characteristic promoter hypermethylation signatures in male germ cell tumors |
title_short | Characteristic promoter hypermethylation signatures in male germ cell tumors |
title_sort | characteristic promoter hypermethylation signatures in male germ cell tumors |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149411/ https://www.ncbi.nlm.nih.gov/pubmed/12495446 http://dx.doi.org/10.1186/1476-4598-1-8 |
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