文章：

寻找视网膜母细胞瘤细胞的起源

The search for the retinoblastoma cell of origin

原文发布日期：2005-02-01

DOI: 10.1038/nrc1545

类型: Review Article

开放获取: 否

要点：

1. Identifying the cell of origin can uncover the initiating and subsequent genetic changes that occur as cells progress from preneoplastic lesions to tumours.
2. Retinoblastoma is a good tumour model for identifying the cell of origin, because retinal development is well understood and the initiating genetic lesion (loss of RB) is well characterized.
3. Models of retinoblastoma differ depending on when RB is thought to act and on the response of the cell of origin to RB loss.
4. Additional mutations, beyond RB disruption, must occur for retinoblastoma to develop. These could occur in genes that regulate programmes of cell death or cell differentiation. New mouse models support the latter possibility.
5. Improved animal models could help to identify the retinoblastoma cell of origin, and explain why retinal cells are especially susceptible to transformation following RB disruption.

要点翻译：

1. 识别细胞起源可揭示细胞从癌前病变进展为肿瘤过程中发生的起始及后续遗传改变。
2. 视网膜母细胞瘤是研究细胞起源的理想肿瘤模型，因为视网膜发育过程已明确，且起始遗传病变（RB基因缺失）已得到充分表征。
3. 视网膜母细胞瘤模型因RB基因的作用时机及起源细胞对RB缺失的反应不同而存在差异。
4. 除RB基因失活外，视网膜母细胞瘤的发展还需其他基因突变，这些突变可能发生在调控细胞死亡或细胞分化程序的基因中。新型小鼠模型支持后一种可能性。
5. 改进的动物模型有助于确定视网膜母细胞瘤的细胞起源，并解释为何视网膜细胞在RB基因失活后特别易发生转化。

英文摘要：

The cellular effects of the genetic defects associated with tumorigenesis are context dependent. To better understand the reasons that different cell types require distinct combinations of mutations to form tumours, it is essential to identify and characterize a tumour's 'cell of origin'. Retinoblastoma, a rare childhood cancer of the retina that is caused by RB inactivation, is a good model in which to search for a tumour cell of origin, because retinal development is well understood and the initiating genetic lesion is well characterized. Identifying the cell of origin for this tumour would advance our understanding of how cellular context affects the requirement of specific mutations for cancer initiation and progression.

摘要翻译： 

与肿瘤发生相关的遗传缺陷的细胞效应是依赖于情境的。为了更好地理解为什么不同类型的细胞需要不同的突变组合才能形成肿瘤，识别并描述肿瘤的“起源细胞”至关重要。视网膜母细胞瘤是一种由RB基因失活引起的罕见儿童视网膜癌症，是寻找肿瘤起源细胞的理想模型，因为视网膜的发育过程已被广泛研究，且其起始遗传病变特征明确。确定这种肿瘤的起源细胞将有助于我们理解细胞情境如何影响癌症起始和进展过程中特定突变的需求。

原文链接：

The search for the retinoblastoma cell of origin