EpiCancer · Comprehensive Platform for the Functional Characterization of Cancer Epigenetics and Diagnosis

Epigenetic regulation of gene expression- the mechanism responsible for establishing and maintaining cellular identities during development- is frequently deregulated in cancer. Our working hypothesis is that this deregulation confers upon cells phenotypic plasticity, resulting in intratumor heterogeneity, which is key to tumor development, metastasis, and drug resistance. In EpiCancer, we seek to provide the technological means to address fundamental issues concerning epigenetics in cancer. Namely, we intend to develop, apply, and validate single-cell and single-molecule epigenetic analysis methods that can parse the function of this network and its heterogeneity in human cancer, and utilize it for cancer diagnosis. We will build a rich arsenal of tools to profile the combinatorial epigenetic network in primary tumors and blood taken from cancer patients at multiple scales of resolution (Aims 1 + 2). We will apply these systems to elucidate the function and connectivity between epigenetic modifications in breast cancer and lymphoma, and link epigenetic heterogeneity to tumor biology and clinical outcome (Aim 3). We will also establish revolutionary systems for cancer diagnostics and monitoring, leveraging the unique advantages of our single-molecule tools for multi-modal analysis of epigenetic, protein biomarkers, and microRNAs, originating from both the tumor and its microenvironment, in patients’ blood (Aims 1 + 3).The epigenetic technologies we intend to provide the scientific community are set to profoundly impact our understanding of the epigenetic determinants of cancer, as well as our ability to detect cancer at early stage from a routine blood test and identify early disease recurrence. The analysis of a large cohort of tumor and blood samples from the same patients will generate novel datasets that are expected to reveal cancer-specific and patient-specific epigenetic modules and shed light on the contribution of epigenetic plasticity to tumor biology.