Program 09 Cancer Genetics

Dana-Farber Cancer Inst, Boston MA

Investigators

Linked publications, trials & patents

Abstract

Cancer Genetics and Epigenetics Program Project Summary / Abstract The overall mission of the DF/HCC Cancer Genetics and Epigenetics Program (CG&E) is to advance and accelerate our understanding of the genetic and epigenetic mechanisms that promote tumorigenesis, then apply this knowledge to improve prevention, screening, diagnosis, and treatment of cancer. The Program’s large and vibrant membership includes investigators with a broad range of scientific interests spanning all major aspects of cancer genetics and epigenetics. Particular areas of focus include: 1) cancer gene discovery and functional characterization; 2) technology development and application (e.g., massively parallel sequencing, emerging genomic technologies, and single cell analyses); 3) computational analysis (e.g., algorithm development, bioinformatics methods, and genome annotation); 4) epigenetic mechanisms of cancer development and progression, including chromatin remodeling, enhancer and promoter hijacking, and transcriptional driver genes; 5) interrogation of resistance mechanisms to cancer targeted therapy, both genetic and epigenetic; 6) clinical cancer genetics, including risk counseling; and 7) delivery of state-of-the-art CLIA- certified testing of both cancer gene panels and of whole exomes for cancer precision medicine. The Program’s 115 members (68 primary and 47 secondary) represent six DF/HCC institutions and 17 academic departments. In 2019, peer-reviewed grant funding attributed to the Program was $9.7 million in direct costs from the NCI and $10.8 million from other sponsors. During the current funding period, primary CG&E members published 1,227 cancer-relevant papers. Of these, 34% were inter-institutional, 11% were intra-programmatic, and 50% were inter-programmatic collaborations between two or more DF/HCC members. These numbers reflect the Program’s extensive interactions with DF/HCC’s clinical, population science, and other basic science Programs, nurtured under the aegis of the Center strategic plan. Since the last CCSG renewal, the emphasis on epigenetic aspects of cancer has expanded considerably, prompting changes in both name (the Program was previously called Cancer Genetics) and leadership (C. KadochDFCI is now one of the three co-Leaders). For the next CCSG funding period, our Specific Aims are to 1) Identify and functionally characterize the full spectrum of cancer driver gene mutations, rearrangements, and amplifications and translate them to enable precision medicine; 2) Determine the chromatin state and epigenetic architecture in multiple cancers, and determine how specific aberrations affect transcription and interact with oncogenic mutations; and 3) Discover the germline, somatic, and chromatin determinants of response and mechanisms of resistance to anticancer therapy, including consideration of tumor heterogeneity, immune cell composition, and the microenvironment. Each Aim will prioritize the cancers most prevalent in the Center’s catchment area.