Quadruplex DNA as biomarker for cancer: studies towards a novel optical diagnostic assay

四链体 DNA 作为癌症生物标志物：新型光学诊断检测方法的研究

• 批准号: 2277959
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2277959
• 关键词: Quadruplex; DNA; biomarker; cancer; studies

Cancer cells are characterized by a high-degree of heterogeneity, which is reflected by the highly variable gene-transcription profiles across tumor tissues. Transcriptional mis-regulation is a hallmark of cancer and is indicative of the aggressiveness of the tumor and its likelihood to respond to therapies. There is an unmet need of general and reliable transcriptional markers that can be used in biopsies to predict response to chemotherapy and to evaluate cancer aggressiveness. DNA G-quadruplexes (G4s) are non-canonical DNA structures that can form in guanine-rich sequences and have recently emerged as promising biomarker of active transcription. Furthermore, immunohistochemistry studies have revealed that G4s are more prevalent in cancer than normal tissues. Therefore, it has been suggested that measurement of global G4s level could be used as cancer biomarker. Herein, we propose to develop a novel set of optical probes to assess G4 levels in biopsies from cancer tissues. These probes will be used to create a 3D G4-map of cancer tissues, followed by transcriptional characterization of the different section of the tissue and genome-wide mapping of chromatin markers providing the first direct correlation between global transcription mis-regulation in cancers and G4s

癌细胞的特征在于高度的异质性，这反映在肿瘤组织中高度可变的基因转录谱上。转录错误调节是癌症的标志，并且指示肿瘤的侵袭性及其对治疗作出响应的可能性。存在对可用于活组织检查以预测对化疗的反应并评估癌症侵袭性的通用且可靠的转录标记物的未满足的需求。DNA G-四链体（G4）是一种非典型的DNA结构，可以在富含鸟嘌呤的序列中形成，最近成为活性转录的有前途的生物标志物。此外，免疫组织化学研究表明，G4在癌症中比正常组织更普遍。因此，已经建议测量总体G4水平可以用作癌症生物标志物。在此，我们建议开发一套新的光学探针来评估来自癌症组织的活检中的G4水平。这些探针将用于创建癌症组织的3D G4图谱，然后对组织的不同部分进行转录表征，并对染色质标记物进行全基因组作图，从而首次将癌症中的全局转录错误调节与G4之间直接关联起来。