Sylvester Comprehensive Cancer Center

Cancer Epigenetics Program

Program Leader(s)

Description of the Program

Epigenetics is the study of phenotypic changes that are not mediated through mutations in DNA sequences. The CE Program is focused on studying epigenetic changes, including modifications in DNA/RNA methylation/hydroxymethylation, histone modifications and the activity of the wide range of non-coding RNAs. There are examples where each component of epigenetic information is deregulated in cancer. Mutations in genes involved in the epigenetic regulation of gene expression have now been found in a broad array of solid tumors and hematologic malignancies. These mutations affect not only DNA methylation and hydroxymethylation, but also the readers, writers and erasers of histone modifications. The discovery of mutations in the histones themselves, e.g. the K to M mutation in histones H3.1 seen in diffuse intrapontine glioma (DIPG) also point to a key role for chromatin structure and function in oncogenesis. Additionally, the discovery of recurring mutations in DNMT3A in myeloid malignancies, as well as clonal hematopoiesis of indeterminate potential (CHIP) and the finding that the TET2 and IDH1/2 mutations occur in a mutually exclusive manner in similar cancers bring the role of these new mechanisms of transformation into focus.

Another important area of investigation within the CE Program is elucidating the mechanisms by which epigenetic regulators orchestrate transcriptional programs in response to growth factor signaling and how such coordination is (de)regulated in cancer. Beyond the well-known binding of epigenetic regulators to their target genes, it was recently revealed that the majority of aberrantly regulated binding sites are distal to genes, occurring at enhancers. Additionally, genome-wide analyses have indicated that mutations in enhancer sequences may be a contributing factor in cancer initiation and progression. These considerations form the basis of studies by a number of the Program members on the diverse mechanisms by which enhancer function is regulated and how such regulation is disrupted in cancer.

Goals of the Program

The Cancer Epigenetics members’ expertise is underscored within the three program Aims, whose objectives are to explore multiple facets of epigenetic regulation in normal and cancer cells.

Epigenetic Regulators Specific Aim: Elucidate the Molecular Mechanisms Underlying Epigenetic Regulators Mutated in Cancer

  • Define the function of epigenetic regulators in cancer initiation and progression.

Signaling to chromatin Specific Aim: Define the downstream effectors of signal transduction pathways converging on chromatin to regulate gene expression in cancer

  • Identify and elucidate the function of key epigenetic targets of aberrant growth signaling in cancer.

Translational epigenetics Specific Aim: Investigate epigenetic targets that explore cancer vulnerabilities and provide diagnostic and therapeutic opportunities

  • Launch personalized epigenetic biomarkers and therapies in pre-clinical and clinical studies.

Participants

E-mail a Friend