Cancer Genetic and Epigenetic Mechanisms

UWCCC CANCER GENETIC AND EPIGENETIC MECHANISMS PROGRAM SUMMARY Co-Leaders: Emery Bresnick and Wei Xu Cancer arises from disruption of genome and epigenome structure and function. Understanding genetic and epigenetic mechanisms and their aberrations will advance cancer prevention, diagnosis, and treatment. The mission of the Cancer Genetic and Epigenetic Mechanisms Program (GEM) is to discover human cancer genetic and epigenetic mechanisms that enable translational science to improve cancer diagnosis, prevention, and therapy. This document illustrates how GEM is vigorously advancing our mission and translating our discoveries to clinical impact. Representative examples include elucidation of oncogenic mechanisms involving genetic and/or epigenetic abnormalities, discovery and interpretation of genetic variants that confer cancer risk, and innovation of enabling systems/tools. GEM mechanistic discoveries have yielded prospective therapeutic targets, which are under evaluation via DT and WARF Therapeutics. Discoveries and translation are achieved via frequent research and precision medicine meetings, pilot projects, leadership facilitation, and faculty recruitment. The GEM program hosts 31 members from 15 departments, which includes basic/translational scientists, clinicians, and data scientists. The GEM program is pursuing three specific aims focusing on cancer types of importance in our catchment area. Aim 1. Elucidate genetic and epigenetic mechanisms to generate translational avenues in oncology. Aim 2. Utilize genetic/epigenetic discoveries to advance human clinical cancer genetics and precision medicine. Aim 3. Innovate unique tools and systems to enable cancer genetic/epigenetic mechanism discovery and translation. GEM members obtained $1.9 million in NCI funding and $6.2 million in other cancer-relevant funding in the last budget year and were highly productive, with 342 total and 125 high-impact (IF >10) publications during the last funding period. Of these publications, 20% resulted from intra-programmatic collaborations, 45% from inter- programmatic collaborations, and 47% from inter-institutional collaborations.