Alternative Cleavage and Polyadenylation Events as Biomarkers

描述(由申请人提供)：外套细胞淋巴瘤(MCL)形成的一个标志性事件是细胞周期蛋白D1基因在Ig增强子下游的移位，导致转录上调。在最具增殖性的MCL中，在存活率最低的患者中，通过交替切割和多聚腺苷酸化(APA)，细胞周期蛋白D13‘非编码区被缩短，从而产生更稳定的对microRNA具有抵抗力的mRNA。我们还将使用最新开发的3P-Seq深度测序技术为MCL定义全球Polya站点选择签名。此外，我们将系统地耗尽已知的切割和多腺苷基化机制的成员，并测试细胞周期蛋白D1聚(A)位点选择的变化。总的来说，从这项提案中收集的信息将提供一幅更清晰的图景 在细胞周期蛋白D1位点和整个基因组上的APA事件。这将提供进一步的诊断标记物，并可能有助于癌症的早期检测。

DESCRIPTION (provided by applicant): A hallmark event in the formation of Mantle Cell Lymphoma (MCL) is the translocation of the cyclin D1 gene downstream of the Ig Enhancer resulting in an upregulation of transcription. In the most proliferative cases of MCL in patients with the lowest survival the cyclin D1 3'UTR is shortened through alternative cleavage and polyadenylation (APA) resulting in a more stable mRNA that is resistant to microRNA. We will also using the newly developed 3P-Seq Deep Sequencing technology to define a global polyA site selection signature for MCL. Also, we will systematically deplete the known members of the cleavage and polyadenylation machinery and test for changes in cyclin D1 poly(A) site selection. Collectively, the information gathered from this proposal will provide a clearer picture of APA events both at the cyclin D1 locus and throughout the genome. This will provide further diagnostic markers and may aid in early cancer detection.