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Characteristic promoter hypermethylation signatures in male germ cell tumors

Sanjay Koul; Jane Houldsworth; Mahesh M. Mansukhani; Alessia Donadio; James M. McKiernan; Victor Reuter; George Bosl; Raju Chaganti; Murty V. Vundavalli

Title:
Characteristic promoter hypermethylation signatures in male germ cell tumors
Author(s):
Koul, Sanjay
Houldsworth, Jane
Mansukhani, Mahesh M.
Donadio, Alessia
McKiernan, James M.
Reuter, Victor
Bosl, George
Chaganti, Raju
Vundavalli, Murty V.
Date:
Type:
Articles
Department(s):
Pathology and Cell Biology
Urology
Volume:
1
Persistent URL:
Book/Journal Title:
Molecular Cancer
Notes:
Germ cell tumor, promoter hypermethylation, MGMT , RASSF1A , BRCA1 , gene expression
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 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.
Subject(s):
Epigenetics
Antioncogenes
Cytology
Pathology
Publisher DOI:
https://doi.org/10.1186/1476-4598-1-8
Item views
47
Metadata:
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Suggested Citation:
Sanjay Koul, Jane Houldsworth, Mahesh M. Mansukhani, Alessia Donadio, James M. McKiernan, Victor Reuter, George Bosl, Raju Chaganti, Murty V. Vundavalli, , Characteristic promoter hypermethylation signatures in male germ cell tumors, Columbia University Academic Commons, .

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