文章：

Wilms肿瘤：关于肿瘤抑制基因、致癌基因和变色龙基因

Wilms' tumours: about tumour suppressor genes, an oncogene and a chameleon gene

原文发布日期：2011-01-20

DOI: 10.1038/nrc3002

类型: Review Article

开放获取: 否

要点：

1. WT1 and WTX seem to function as tumour suppressor genes (TSGs) in Wilms' tumours, but questions have arisen about these labels.
2. The lack of an increased frequency of Wilms' tumours or other malignancies in patients with osteopathia striata congenita with cranial sclerosis (OSCS) with WTX germline mutations initially challenged its designation as a TSG, but a recent observation of Wilms' tumour precursor lesions in a patient with OSCS supports this label.
3. In Wilms' tumours, WT1 conforms to a TSG label: patients heterozygous for WT1 germline mutations are predisposed to Wilms' tumour and WT1 is inactivated in tumours. These data link loss of WT1 function with enhanced cell viability and/or proliferation.
4. By contrast, ablation of WT1 at the initial stages of kidney development results in apoptosis and renal agenesis, indicating that it has a crucial role in maintaining cell viability.
5. In some leukaemias, the increased expression of WT1 compared with normal bone marrow cells, along with some reports of WT1 expression being a marker of poor prognosis, suggest that WT1 functions as an oncogene. By contrast, observations of WT1 inactivating mutations in leukaemias suggest it functions as a TSG.
6. WT1 has important roles in regulating normal differentiation in various organs and cell types. During both nephrogenesis and haematopoiesis, loss of WT1 or overexpression of WT1 is associated with differing phenotypic consequences, depending on the differentiation status of the cell.
7. The oncogenic or tumour suppressive effect of WT1 alteration is likely to be a result of how a cell at a particular stage of development responds to perturbations in normal differentiation. In short, either label may be misleading and/or inadequate when used to describe the function of WT1.

要点翻译：

1. WT1和WTX在肾母细胞瘤中似乎起着肿瘤抑制基因（TSG）的作用，但这些标签也引发了质疑。
2. 患有先天性条纹状骨病伴颅骨硬化症（OSCS）且携带WTX种系突变的患者，其肾母细胞瘤或其他恶性肿瘤的发生频率并未增加，这一现象最初对其作为TSG的定位提出了挑战，但最近在一名OSCS患者中观察到肾母细胞瘤前驱病变，支持了这一标签。
3. 在肾母细胞瘤中，WT1符合TSG的标签：携带WT1种系突变杂合子的患者易患肾母细胞瘤，且WT1在肿瘤中失活。这些数据将WT1功能丧失与细胞存活和/或增殖增强联系起来。
4. 相比之下，在肾脏发育的初始阶段消除WT1会导致细胞凋亡和肾发育不全，表明其在维持细胞存活中起着关键作用。
5. 在某些白血病中，与正常骨髓细胞相比，WT1的表达增加，加之一些报道称WT1表达是预后不良的标志物，表明WT1起着癌基因的作用。然而，在白血病中观察到WT1失活突变又提示其可能作为TSG发挥作用。
6. WT1在调节多种器官和细胞类型的正常分化中具有重要作用。在肾发生和造血过程中，WT1的缺失或过度表达会因细胞分化状态的不同而产生不同的表型后果。
7. WT1改变的致癌或肿瘤抑制效应可能是特定发育阶段的细胞对正常分化扰动的一种反应。简言之，无论使用哪种标签来描述WT1的功能，都可能具有误导性和/或不准确性。

英文摘要：

Genes identified as being mutated in Wilms' tumour include TP53, a classic tumour suppressor gene (TSG); CTNNB1 (encoding β-catenin), a classic oncogene; WTX, which accumulating data indicate is a TSG; and WT1, which is inactivated in some Wilms' tumours, similar to a TSG. However, WT1 does not always conform to the TSG label, and some data indicate that WT1 enhances cell survival and proliferation, like an oncogene. Is WT1 a chameleon, functioning as either a TSG or an oncogene, depending on cellular context? Are these labels even appropriate for describing and understanding the function of WT1?

摘要翻译： 

在Wilms瘤中被发现发生突变的基因包括：TP53，这是一个经典的肿瘤抑制基因（TSG）；CTNNB1（编码β-连环蛋白），这是一个经典的原癌基因；WTX，越来越多的数据表明它是一个TSG；以及WT1，它在某些Wilms瘤中失活，类似于TSG。然而，WT1并不总是符合TSG的标签，一些数据表明WT1像原癌基因一样增强细胞存活和增殖。WT1是一个变色龙吗，根据细胞环境的不同，既可以作为TSG也可以作为原癌基因？这些标签对于描述和理解WT1的功能是否合适？

原文链接：

Wilms' tumours: about tumour suppressor genes, an oncogene and a chameleon gene