（5.18）The Role of Noncoding Alterations in Cancer Genome
报告题目：The Role of Noncoding Alterations in Cancer Genome
Somatic copy number alterations are central events in cancer pathogenesis. Gene-centric analysis of focal amplification events has identified many oncogenes. However, for focal amplifications that occur outside of coding regions, the identity of specific targets has remained unclear. By combining copy number data with epigenomic profiling, we found six focally amplified non-coding regions harboring super-enhancers near oncogenes such as MYC. We applied CRISPR/Cas9-mediated enhancer repression methods to reveal the role of the focally amplified super-enhancers in activating MYC expression and promoting tumorigenesis. Our methods also identified a novel candidate oncogene KLF5. In addition to noncoding super-enhancer amplifications, we found the KLF5 gene is also subject to hotspot missense mutations. We revealed that these genomic alterations activate KLF5 by increasing the transcription, enhancing the stability or altering the DNA binding specificity of KLF5.
Dr. Zhang graduated in 2008 from the department of biology,Fudan University. He obtained his PhD degree in genetics in 2013 atDartmouth College. In 2013 Dr. Zhang joined as a research fellow at the laboratory of Matthew Meyerson, Department of Medical Oncology, Dana-Farber Cancer Institute/Harvard Medical School. He also worked as a Visiting research fellow, Cancer Program, Broad Institute of MIT and Harvard .Dr Zhang has published a number of papers in top journals such as Nature Genetics, Nature Communications, Trends in Genetics and Genome research. His most recent research focuses on cancer genomics, cancer epigenetics and genome editing.