Both genetic and epigenetic mutations contribute to human cancers. Mutations in oncogenes, tumor suppressor genes, and DNA repair genes have been identified in human cancers. Epigenetic mutations such as methylation of tumor suppressor genes and DNA repair genes and loss of imprinting of IGF2 gene are also associated with cancers. The major goal of my research is to identify cancer genes and epigenetic markers for human cancers. Rapid progress in human genome project has significantly speeded up the discovery in genetic research and disease research. Sequence analysis and bioinformatics play a vital role in understanding genetic basis of human diseases. One of my major interest is to apply bioinformatics to genetic research. Positional cloning and candidate cloning of cancer genes. We have generated transcript maps for regions showing loss of heterozygosity (LOH) at 13q11 in esophageal cancer. Mutational analysis of candidate genes in the human chromosome 13q11 have been carried out to identify tumor suppressor genes. We are also taking candidate gene cloning approach to analyze several hundreds of genes involved in cancers such as oncogene, tumor suppressor genes, and DNA repair genes. We are performing mutational analysis as well as methylation of CpG island in the promoter region of these cancer genes. In addition, altered gene expression in tumors will be analyzed by methods such as Affymetrix expression chip. Genome-wide search of imprinted genes. We have used transcribed single nucleotide polymorphism (SNP) to isolate several imprinted genes. We are using Affymetrix chip to genotype DNA and to quantitatively analyze the allele-specific gene expression. Similarly, we will systematically isolate epigenetic markers. We will examine both the imprinted genes and epigenetic markers in tumors and their matched normal tissues and in populations with high and low risk of cancer. The alteration in imprinting will be analyzed for its association with other genetic changes such as genomic instability, mutations in cancer genes, and genotype.
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