Cancer Genomics and Epigenomics

Case Western Reserve University, Cleveland OH

Investigators

Linked publications & trials

Abstract

CANCER GENOMICS AND EPIGENOMICS PROGRAM PROJECT SUMMARY/ABSTRACT The Cancer Genomics and Epigenomics (CGE) Program is a basic discovery program with a strong translational focus. The overarching goals of the CGE program are to discover and understand the genetic and epigenetic alterations that contribute to cancer, and to translate these discoveries towards early detection and treatment of cancer. The program is organized around 3 scientific aims: 1) Discover germline and somatic genetic alterations and elucidate the mechanisms by which these alterations drive tumorigenesis; 2) Discover novel epigenetic or epigenomic regulators of cancer; 3) Translate genetic and epigenetic discoveries for cancer diagnosis and therapy. Supported by pilot funding from Case CCC, CGE has strategically invested in cutting-edge technologies such as single-cell and spatial genomic approaches, epigenome and 3D genome mapping tools, computational and system biology pipelines, and high-throughput genome and epigenome editing methods. Research conducted by CGE members reflects the focus of our catchment area with a goal of delivering exceptional cancer care to our community. CGE members also actively engage in Community Outreach and Engagement (COE) and Cancer Research Training and Education Coordination (CRTEC) activities. Under the leadership of PLs Zhenghe (John) Wang and Fulai Jin, CGE has 33 full members representing 13 departments across all three consortium institutions. Current cancer relevant funding is over $10M (direct), including $3.4M from NCI. The program's continuing momentum is reflected and assured by its multi-investigator teams that have successfully competed for an Esophageal cancer P01, GI SPORE, BETRNet, EDRN, U01, U54, SU2C dream team award, and multi-PI R01s. During the current cycle, CGE members published 563 cancer-related publications (37% in journals with impact factors >10), including 41% Inter- and 16% intra-programmatic publications. This highly productive program has made paradigm-shifting discoveries and successfully translated some discoveries into clinical practice or clinical trials through inter-programmatic hand-off. Examples include: 1) identification of germline WWP1 mutations causing PTEN wild-type hamartoma syndrome; 2) discovery of enhancer elements present in extrachromosomal DNAs that increasing oncogene expression such as EGFR in glioblastoma; 3) development of highly innovative tools for cancer genomic and epigenomic research, such as big-data integration, 3-D genome architecture, and RNA biology; 4) FDA approved sampling device (EsoCheck) and methyl-DNA assay (EsoGuard) for the early detection of esophageal cancer; 5) phase I and II clinical trials based on the discovery of glutamine addiction of PIK3CA-mutant colorectal cancers; 6) a clinical trial to test the combination of PI3K and EZH2 inhibitors in tumors harboring PIK3CA helical domain mutation based on the discovery of a synergy between the two pathways. 8) a clinical trial to test TGF-β inhibitor in esophageal cancer based on the discovery that the TGF-β pathway is activated in most esophageal cancers.