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The Korean Journal of Pathology 2007;41(1): 21-29.
Methylation Patterns of Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) Related to the Germ Cell Differentiation of Human Germ Cell Tumors.
Sun Young Jun, Kyu Rae Kim, Jene Choi, Jae Y Ro
1Department of Pathology, Hallym University Sacred Heart Hospital, Anyang, Korea.
2Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Korea. krkim@amc.seoul.kr
3Department of Pathology, The Methodist Hospital, Houston, Texas, USA.
ABSTRACT
BACKGROUND: The histogenesis and interrelationship of the various types of germ cell tumors (GCTs) have been proposed. Dysgerminoma/seminoma (D/S) is a primitive GCT that has not acquired the potential for further differentiation, whereas other types of GCTs are in a dynamic process of differentiation towards a somatic or extraembryonal direction. A primordial germ cell giving rise to a GCT undergoes a developmentally regulated erasure and resetting of imprinted genes, but changes in the imprinting pattern in GCTs as the tumor differentiates have not been well defined. We aimed to investigate the changes of the SNRPN methylation pattern between the germinomas and non-germinomatous GCTs, as compared with the somatic methylation pattern. METHODS: We used formalin-fixed paraffin-embedded tissue sections of 97 GCTs (18 Ds, 21 Ss, 17 yolk sac tumors (YSTs), 19 immature teratomas, and 22 mature teratomas). DNA methylation was evaluated after bisulfite modification, PCR amplification, and restriction enzyme digestion. RESULTS: The SNRPN methylation pattern was changed in 53/74 (71.6%) of GCTs as non-somatic patterns. There were significant differences in the methylation pattern between the germinomas and non-germinomatous GCTs, the GCTs being frequently hypo- methylated in Ds/Ss (73.3%), in contrast to the frequent hypermethylation seen in the YSTs and teratomas (47.7%, p<0.05). CONCLUSIONS: The methylation status of an imprinting gene may be involved in the mechanism causing cellular differentiation and tumorigenesis of GCTs.
Key Words: Neoplasms, Germ cell, Embryonal; Genomic imprinting; Small nuclear ribonucleoprotein polypeptide N(SNRPN)
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