High-throughput microRNAome analysis in human germ cell tumours
High-throughput microRNAome analysis in human germ cell tumours
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DOI：
10.1002/path.2230
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发表时间：
2007-11-01
影响因子：
7.3
通讯作者：
Looijenga, L. H. J.
中科院分区：
文献类型：
--
作者：
Gillis, A. J. M.;Stoop, H. J.;Looijenga, L. H. J.
青少年和成年人的睾丸生殖细胞肿瘤（GCT）可细分为腺瘤（称为卵巢无性细胞瘤）和非腺瘤，均称为11型GCT。它们起源于原位癌（CIS），是原始生殖细胞（PGCs）/生殖细胞的恶性对应物。侵入性成分模拟胚胎发生，包括干细胞成分胚胎癌（EC）、体细胞谱系畸胎瘤（TE）和胚胎外组织卵黄囊瘤（YST）和绒毛膜癌（CH）。另一种类型是所谓的精细胞精原细胞瘤（SS，III型GCT），由肿瘤性初级精母细胞组成。我们以前报道过，miRNAs hsa-miR 371-373簇参与抑制致癌应激诱导的细胞衰老，使细胞恶性化。在这里，我们报告了第一个高通量筛选的156 microRNA在一系列的II型和III型GCT（n = 69，一式两份）使用定量PCR为基础的方法。在标准化以允许样本间分析后，技术重复聚类在一起，并且先前的hsa-miRNA 371-373聚类发现得到证实。无监督聚类分析表明，细胞系与体内样品不同。正常和恶性的体内样品主要基于它们的成熟状态聚类。这与正常的胚胎发生相类似，而不是肿瘤中的染色体异常。单个簇内的miRNAs表现出相似的表达模式，这意味着共同的调控机制。正常睾丸组织表达最具鉴别力的miRNA，其水平高于SE和SS。此外，分化的非胶质瘤显示出识别性miRNA的过表达。这些结果支持了miRNAs参与调控保留在GCT中的干细胞分化的模型。版权所有（C）2007英国和爱尔兰病理学会。由John Wiley & Sons有限公司出版
Testicular germ cell tumours (GCTs) of adolescents and adults can be subdivided into seminomas (referred to as dysgerminomas of the ovary) and non-seminomas, all referred to as type 11 GCTs. They originate from carcinoma in situ (CIS), being the malignant counterparts of primordial germ cells (PGCs)/gonocytes. The invasive components mimic embryogenesis, including the stem cell component embryonal carcinoma (EC), the somatic lineage teratoma (TE), and the extra-embryonic tissues yolk sac tumour (YST) and choriocarcinoma (CH). The other type is the so-called spermatocytic seminomas (SS, type III GCT), composed of neoplastic primary spermatocytes. We reported previously that the miRNAs hsa-miR 371-373 cluster is involved in overruling cellular senescence induced by oncogenic stress, allowing cells to become malignant. Here we report the first high-throughput screen of 156 microRNAs in a series of type II and III GCTs (n = 69, in duplicate) using a quantitative PCR-based approach. After normalization to allow inter-sample analysis, the technical replicates clustered together, and the previous hsa-miRNA 371-373 cluster finding was confirmed. Unsupervised cluster analysis demonstrated that the cell lines are different from the in vivo samples. The in vivo samples, both normal and malignant, clustered predominantly based on their maturation status. This parallels normal embryogenesis, rather than chromosomal anomalies in the tumours. miRNAs within a single cluster showed a similar expression pattern, implying common regulatory mechanisms. Normal testicular tissue expressed most discriminating miRNAs at a higher level than SE and SS. Moreover, differentiated non-seminomas showed overexpression of discriminating miRNAs. These results support the model that miRNAs are involved in regulating differentiation of stem cells, retained in GCTs. Copyright (C) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.