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

癌细胞具有高度的异质性，这反映在肿瘤组织中高度可变的基因转录谱上。转录调控错误是癌症的一个标志，表明肿瘤的侵袭性及其对治疗的反应可能性。在活组织检查中用于预测化疗反应和评估癌症侵袭性的通用和可靠的转录标记物的需求尚未得到满足。DNA g -四重构象（G4s）是一种非规范的DNA结构，可以在富含鸟嘌呤的序列中形成，近年来作为一种有前景的生物标记物出现。此外，免疫组织化学研究表明，G4s在癌症中比在正常组织中更普遍。因此，有人建议测量G4s的整体水平可以作为癌症的生物标志物。在此，我们建议开发一套新的光学探针来评估癌症组织活检中的G4水平。这些探针将用于创建癌症组织的3D g4图谱，随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定位，从而首次提供癌症中全局转录调控错误与g4之间的直接关联

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