Mature and immature ovarian teratomas share methylation profiles of imprinted genes: a MS-MLPA analysis
Mature and immature ovarian teratomas share methylation profiles of imprinted genes: a MS-MLPA analysis
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DOI：
10.1007/s00428-023-03491-z
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发表时间：
2023-01-13
期刊：
影响因子：
3.5
通讯作者：
Kurotaki，Hidekachi
中科院分区：
文献类型：
--
作者：
Kato，Noriko;Kamataki，Akihisa;Kurotaki，Hidekachi
未成熟畸胎瘤是卵巢畸胎瘤的一个亚类，成熟和未成熟卵巢畸胎瘤之间的致病关系尚不清楚。成熟卵巢畸胎瘤是由单个卵母细胞/卵子产生的孤雌生殖肿瘤，而未成熟卵巢畸胎瘤的起源尚未得到广泛研究。由于单性生殖肿瘤只包含母体基因组，这些肿瘤中的基因组印记通常遵循母体模式。DNA甲基化是基因组印迹的重要机制之一。因此，我们分析了印迹基因的甲基化谱进行甲基化特异性的多重连接依赖探针扩增（MS-MLPA）的25印迹控制区（ICR）在10个印迹基因/基因簇福尔马林固定，石蜡包埋的样品从4个未成熟卵巢畸胎瘤，8个成熟卵巢畸胎瘤，和4个卵巢卵黄囊肿瘤（YST）。在未成熟畸胎瘤的每个ICR中，未成熟和成熟组分均显示出相似的甲基化水平。总的来说，未成熟卵巢畸胎瘤表现出与其孤雌生殖起源一致的印记基因的母体甲基化模式。然而，他们也在一些印记基因中显示出异常的甲基化水平，这表明未成熟畸胎瘤中的基因组印记可能与成熟畸胎瘤中的基因组印记部分不同。在一个未成熟畸胎瘤中观察到YST的显微镜病灶; YST组分也显示出母体甲基化模式，不像纯YST显示出不规则的模式。因此，畸胎瘤相关的YST和单纯的YST可能有不同的致病机制。
Immature teratomas are a subset of ovarian teratomas, and the pathogenic relationship between mature and immature ovarian teratomas is unclear. Mature ovarian teratomas are parthenogenetic tumors that arise from a single oocyte/ovum, whereas the origin of immature ovarian teratomas has not been extensively investigated. Since parthenogenetic tumors contain only maternal genomes, genome imprinting in these tumors usually follows a maternal pattern. DNA methylation is among the most important mechanisms of genome imprinting. Therefore, we analyzed the methylation profile of imprinted genes by performing methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of 25 imprinting control regions (ICRs) in 10 imprinted genes/gene clusters from formalin-fixed, paraffin-embedded samples obtained from 4 immature ovarian teratomas, 8 mature ovarian teratomas, and 4 ovarian yolk sac tumors (YSTs). Both the immature and mature components showed similar methylation levels in each ICR in immature teratomas. Overall, immature ovarian teratomas showed maternal methylation patterns of imprinted genes in concordance with their parthenogenetic origin. However, they also showed aberrant methylation levels in a few imprinted genes, suggesting that genome imprinting in immature teratomas may partially differ from that in mature teratomas. Microscopic foci of YST were seen in one immature teratoma; the YST component also showed a maternal methylation pattern, unlike the pure YSTs that showed irregular patterns. Thus, teratoma-associated YST and pure YST may have different pathogenic mechanisms.