New evidence for the origin of intracranial germ cell tumours from primordial germ cells: expression of pluripotency and cell differentiation markers
New evidence for the origin of intracranial germ cell tumours from primordial germ cells: expression of pluripotency and cell differentiation markers
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DOI：
10.1002/path.1948
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发表时间：
2006-05-01
影响因子：
7.3
通讯作者：
Rajpert-De Meyts, E
中科院分区：
文献类型：
--
作者：
Hoei-Hansen, CE;Sehested, A;Rajpert-De Meyts, E
原发性颅内生殖细胞肿瘤是发生在儿童和青少年中的罕见肿瘤。这项研究检查了这些肿瘤的生物学和起源，因为人们假设它们起源于全能原始生殖细胞。我们应用了性腺生殖细胞肿瘤的最新知识，并分析了一系列干细胞相关蛋白（C-KIT，OCT-3/4（POU 5 F1），AP-2 γ（TFAP 2C）和NANOG）和发育调节生殖细胞特异性蛋白（包括MAGE-A4，NY-ESO-1和TSPY）的表达。在蛋白质水平的表达进行了分析，在21名儿童和年轻人与颅内生殖细胞瘤和非生殖细胞瘤，有助于这些不寻常的肿瘤的仔细描述，并增加了对发病机制的理解。干细胞相关蛋白在颅内生殖细胞肿瘤中高度表达，并且检测到与其性腺等效物的许多相似之处，包括与原始生殖细胞的密切相似之处。一个显着的差异是性别特异性表达的TSPY，一个基因以前牵连的起源性腺母细胞瘤。TSPY仅在雄性中枢神经系统（CNS）的生殖细胞肿瘤中检出，表明其不是恶性生殖细胞转化启动所必需的。CNS生殖细胞肿瘤中与胚胎干细胞多能性相关的基因的表达强烈表明，这些肿瘤源自至少部分保留胚胎干细胞样表型的细胞，这是原始生殖细胞的标志。版权所有（c）2006大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Primary intracranial germ cell tumours are rare neoplasms that occur in children and adolescents. This study examined both the biology and the origin of these tumours, as it has been hypothesized that they originate from a totipotent primordial germ cell. We applied recent knowledge from gonadal germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2 gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected with their gonadal equivalents, including a close similarity with primordial germ cells. A notable difference was the sex-specific expression of TSPY, a gene previously implicated in the origin of gonadoblastoma. TSPY was only detected in germ cell tumours in the central nervous system (CNS) from males, suggesting that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which is a hallmark of primordial germ cells. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.