Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma
Distinct Gene Expression Profiles Define Anaplastic Grade in Retinoblastoma
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DOI：
10.1016/j.ajpath.2018.06.013
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发表时间：
2018-10-01
影响因子：
6
通讯作者：
Grossniklaus, Hans E.
中科院分区：
文献类型：
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作者：
Hudson, Lauren E.;Mendoza, Pia;Grossniklaus, Hans E.
近几十年来，与视网膜母细胞瘤相关的发病率和死亡率急剧下降，这在很大程度上是由于对高危疾病的更好预测和适当的治疗分层。高风险的组织病理学特征和严重的间变性都预示着需要更积极的治疗;然而，并非所有中心都能够轻松评估肿瘤样本的间变性程度。相反，识别能够区分间变性等级并因此预测高风险与低风险视网膜母细胞瘤的遗传特征将有助于在更广泛的患者人群中进行适当的风险分层。更好地了解在间变性中失调的基因也将对更严重的视网膜母细胞瘤发展的潜在途径产生有价值的见解。在这里，我们提出了28例视网膜母细胞瘤的组织病理学和基因表达分析，使用微阵列分析。不同间变性等级的肿瘤显示出明显的差异基因表达，在严重间变性中具有独特基因和途径的显著失调。光感受器和核孔蛋白的表达特别被鉴定为在严重的间变性中高度失调，并表明有助于视网膜母细胞瘤严重程度增加的发展的特定细胞过程。在我们的数据集中，一组有限的高度差异表达的基因也能够准确地预测严重的间变性。总之，这些数据有助于了解间变性的发展，并促进高风险视网膜母细胞瘤的遗传标记的识别。
Morbidity and mortality associated with retinoblastoma have decreased drastically in recent decades, in large part owing to better prediction of high-risk disease and appropriate treatment stratification. High-risk histopathologic features and severe anaplasia both predict the need for more aggressive treatment; however, not all centers are able to assess tumor samples easily for the degree of anaplasia. Instead, identification of genetic signatures that are able to distinguish among anaplastic grades and thus predict high- versus low-risk retinoblastoma would facilitate appropriate risk stratification in a wider patient population. A better understanding of genes dysregulated in anaplasia also would yield valuable insights into pathways underlying the development of more severe retinoblastoma. Here, we present the histopathologic and gene expression analysis of 28 retinoblastoma cases using microarray analysis. Tumors of differing anaplastic grade show clear differential gene expression, with significant dysregulation of unique genes and pathways in severe anaplasia. Photoreceptor and nucleoporin expression in particular are identified as highly dysregulated in severe anaplasia and suggest particular cellular processes contributing to the development of increased retinoblastoma severity. A limited set of highly differentially expressed genes also are able to predict severe anaplasia accurately in our data set. Together, these data contribute to the understanding of the development of anaplasia and facilitate the identification of genetic markers of high risk retinoblastoma.