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

癌细胞的特点是高度异质性，这反映在肿瘤组织中高度不同的基因转录谱上。转录错误调控是癌症的一个标志，它表明了肿瘤的侵袭性及其对治疗的反应的可能性。有一个尚未满足的普遍和可靠的转录标记物的需求，可用于活检，以预测化疗的反应和评估癌症的侵袭性。DNA G-四联体(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，最近被认为是活跃转录的生物标志物。此外，免疫组织化学研究表明，G4S在癌症组织中比正常组织中更常见。因此，对全球G4S水平的测定可以作为肿瘤的生物标志物。在此，我们建议开发一套新的光学探针来评估来自癌症组织的活检组织中的G4水平。这些探针将被用来创建癌症组织的3D G4图谱，随后将对组织的不同部分进行转录鉴定，并在全基因组范围内绘制染色质标记图，从而首次在癌症中的全球转录错误调控与G4S之间建立直接关联

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