Recent advances in retinoblastoma genetic research
Recent advances in retinoblastoma genetic research
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DOI：
10.1097/icu.0b013e32832f7f25
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发表时间：
2009-09-01
影响因子：
3.7
通讯作者：
Ganguly, Arupa
中科院分区：
文献类型：
--
作者：
Nichols, Kim E.;Walther, Susan;Ganguly, Arupa
综述视网膜母细胞瘤是一种儿科眼部肿瘤，为了解癌症的遗传学基础提供了一个范例。这篇综述将重点介绍视网膜母细胞瘤遗传学研究的最新进展，并讨论这些新发现如何影响我们对视网膜母细胞瘤发生和治疗的认识。最近的发现目前的数据表明，视网膜母细胞瘤患者中发现的良性视网膜肿瘤，表现出视网膜母细胞瘤基因RB1的双等位基因突变，并且缺乏视网膜母细胞瘤蛋白的表达。有趣的是，视网膜细胞瘤表现出低水平的基因组不稳定，在视网膜母细胞瘤中逐渐变得更加严重。此外，视网膜母细胞瘤的基因组改变与视网膜母细胞瘤相似。总的来说，这些数据表明视网膜瘤是真正的癌前病变，而不是先前认为的退行性视网膜母细胞瘤肿瘤。视网膜母细胞瘤遗传学研究的翻译性进展包括发展了一种等位基因特异性分析，现在可以鉴定突变嵌合体，从而将双侧视网膜母细胞瘤患者中RB1突变的检测率提高到95%。这些和相关的研究工作揭示了新的数据，增强了我们对视网膜母细胞瘤生物学的理解。这些观察可能促进新的治疗方法，以进一步降低与视网膜母细胞瘤和其他更常见形式的癌症相关的发病率和死亡率。
Purpose of reviewRetinoblastoma is a pediatric eye tumor that serves as a paradigm for understanding the genetic basis of cancer. This review will highlight recent advances in retinoblastoma genetic research and discuss how these new findings influence our knowledge of retinoblastoma tumorigenesis and management.Recent findingsCurrent data demonstrate that retinomas, benign retinal tumors found in some retinoblastoma patients, exhibit bi-allelic mutations in RB1, the retinoblastoma gene, and lack of expression of the retinoblastoma protein. Interestingly, retinomas demonstrate a low level of genomic instability that becomes progressively more severe in retinoblastoma tumors. Additionally, a subset of retinomas share genomic alterations with retinoblastoma. Collectively, these data suggest that retinomas represent true premalignant lesions and not regressed retinoblastoma tumors, as previously thought. Translational advances in retinoblastoma genetic research include development of an allele-specific assay that now enables the identification of mutational mosaicism, thereby increasing the rate of RB1 mutation detection in bilaterally affected patients to as high as 95%.SummaryThese and related research efforts reveal novel data that enhance our understanding of the biology of retinoblastoma. These observations may facilitate new therapeutic approaches to further decrease the morbidity and mortality associated with retinoblastoma and other more common forms of cancer.