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

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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