Alternative Cleavage and Polyadenylation Events as Biomarkers

描述（由申请人提供）：套细胞淋巴瘤（MCL）形成过程中的一个标志性事件是Ig增强子下游的cyclin D1基因易位导致转录上调。在生存期最低的MCL患者中，细胞周期蛋白D1 3'UTR通过选择性切割和聚腺苷化（APA）被缩短，从而产生更稳定的mRNA，对microRNA具有抗性。我们还将使用新开发的3P-Seq深度测序技术来定义MCL的全局polyA位点选择签名。此外，我们将系统地耗尽已知的切割和聚腺苷酸化机制成员，并测试细胞周期蛋白D1聚(A)位点选择的变化。总的来说，从这个建议中收集到的信息将提供一个更清晰的画面

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.