Department of Anatomic Pathology, Hirosaki University School of Medicine and Hospital, Hirosaki, Japan.
Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
J Pathol. 2021 Aug;254(5):567-574. doi: 10.1002/path.5702. Epub 2021 Jun 2.
Mucinous ovarian tumours are sometimes associated with mature teratomas. It is suggested that the mucinous tumours in this setting are derived from teratomas, but there remains the possibility of collision or metastasis from extra-ovarian sites. Because mature ovarian teratomas are considered to be parthenogenetic tumours that arise from a single oocyte/ovum, they have only a maternal genome and therefore show maternal genome imprinting. If mucinous ovarian tumours originate from teratomas, their genome imprinting is theoretically maternal. One of the most important mechanisms of genome imprinting is DNA methylation. In the present study, we analysed a total of 28 mucinous ovarian tumours (7 with teratomas, 21 without teratomas; 14 malignant, 14 borderline) to clarify the methylation profiles of their imprinted genes using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) of 21 imprinting control regions (ICRs) of nine imprinted genes/gene clusters using formalin-fixed, paraffin-embedded samples. All cases lacked evidence of an extra-ovarian primary mucinous tumour. In all seven mucinous tumours with teratomas, the overall methylation profile of mucinous tumours was comparable to that of teratomas, although some ICRs showed aberrant methylation. In contrast, all but one of the mucinous tumours without teratomas showed somatic or irregular methylation patterns. Morphologically, there was little teratomatous tissue in some mucinous tumours carrying teratoma-type methylation profiles, suggesting that mucinous tumours overwhelmed ancestral teratomas. In conclusion, the methylation profile of imprinted genes provides evidence that a subset of mucinous ovarian tumours originated from mature teratomas. Genome imprinting-based analysis is a promising strategy to verify the teratomatous origin of human tumours. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
黏液性卵巢肿瘤有时与成熟畸胎瘤有关。有人认为，这种情况下的黏液性肿瘤来源于畸胎瘤，但也不能排除来自卵巢外部位的碰撞或转移的可能性。由于成熟的卵巢畸胎瘤被认为是单卵/卵子起源的部分合生肿瘤，它们只有一个母系基因组，因此表现出母系基因组印记。如果黏液性卵巢肿瘤起源于畸胎瘤，那么它们的基因组印记理论上是母系的。基因组印记的最重要机制之一是 DNA 甲基化。在本研究中，我们分析了总共 28 例黏液性卵巢肿瘤（7 例伴畸胎瘤，21 例无畸胎瘤；14 例恶性，14 例交界性），使用福尔马林固定、石蜡包埋样本的 21 个印迹控制区（ICRs）的 9 个印迹基因/基因簇的甲基化特异性多重连接依赖性探针扩增（MS-MLPA）来阐明印迹基因的甲基化谱。所有病例均缺乏卵巢外原发性黏液性肿瘤的证据。在所有 7 例伴畸胎瘤的黏液性肿瘤中，尽管一些 ICR 显示出异常甲基化，但黏液性肿瘤的总体甲基化谱与畸胎瘤相似。相比之下，所有无畸胎瘤的黏液性肿瘤中除 1 例外均显示出体性或不规则的甲基化模式。形态学上，一些携带畸胎瘤样甲基化谱的黏液性肿瘤中只有少量的畸胎瘤组织，这表明黏液性肿瘤压制了原始的畸胎瘤。总之，印迹基因的甲基化谱为一部分黏液性卵巢肿瘤起源于成熟畸胎瘤提供了证据。基于基因组印记的分析是验证人类肿瘤的畸胎瘤起源的一种很有前途的策略。© 2021 大不列颠及爱尔兰病理学学会。由 John Wiley & Sons, Ltd 出版。
