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인체배아세포종양에서 세포분화에 따른 SNRPN 각인유전자 메틸화의 변화

Methylation Patterns of Small Nuclear RibonucleoproteinPolypeptide N (SNRPN) Related to the Germ Cell Differentiationof Human Germ Cell Tumors

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참고문헌

주제분류병리학

초록

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 hypomethylated 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.

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