Research

Cancer is a disease of impaired genetic and epigenetic integrity. The goal of our research project is to determine the genetic and genomic factors regulating widespread alterations occurred in cancer genomes.

Among the genetic changes in cancer genomes, gene amplification in particular has significant clinical implications, since gene amplification is often associated with poor prognosis. In most cases, the ‘gene' amplification involves large genomic regions that span several mega bases of DNA. We have determined a molecular mechanism for a large DNA palindrome formation that initiates gene amplification in mammalian cells. Using a new microarray-based approach (Genome-wide Analysis of Palindrome Formation, GAPF) we have also shown that palindrome formation is widespread and non-randomly distributed in cancer genome that provides a structural platform for subsequent gene amplification. Further systematic genomic and molecular approaches will allow us to determine genomic and genetic factors regulating palindrome formation.

DNA methylation in mammals is a well-established epigenetic mechanism that controls a variety of important developmental functions. Cytosine DNA methylation predominantly occurs at CpG dinucleotides, of which more than 70% are methylated. CpG islands are clusters of CpG dinucleotides that mostly remain unmethylated for gene regulation. Although CpG islands are generally considered to be unmethylated, a significant fraction of CpG islands can be methylated. Examples include the differential methylation of promoter CpG islands for the transcriptional repression of tumor suppressor genes in cancer cells. A robust, genome-wide assessment of CpG island methylation will determine important epigenetic controls during tissue differentiation and carcinogenesis.

These studies will elucidate the mechanisms for the evolution of cancer genome and individual the susceptibility of individuals to cancer, which ultimately leads to novel diagnostic and therapeutic measures against cancer.