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.Positional cloning and candidate cloning of cancer genes. We have generated transcript maps for regions showing loss of heterozygosity (LOH) in hepatocellular carcinoma and esophageal cancer. Mutational analysis of candidate genes in the LOH region will be carried out to identify tumor suppressor genes. We are in the process to isolate DNA repair genes that will be analyzed for the presence of mutations in tumors. In addition, altered gene expression in tumors will be analyzed by methods such as cDNA microarray and Affymetrix chip. Genome-wide search of imprinted genes. We have used transcribed single nucleotide polymorphism (SNP) to isolate several imprinted genes. We will exploit large collection of transcribed SNP to isolate imprinted genes. High throughput methods such as real-time polymerase chain reaction (PCR), Affymetrix chip, and MassSpec will be used 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.

National Institute of Health (NIH)
Division of Cancer Epidemiology And Genetics (NCI)
Intramural Research (Z01)
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Cancer Epidemiology and Genetics
United States
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Hu, Nan; Kadota, Mitsutaka; Liu, Huaitian et al. (2016) Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer. Cancer Res 76:1714-23
Kadota, Mitsutaka; Sato, Misako; Duncan, Beverly et al. (2009) Identification of novel gene amplifications in breast cancer and coexistence of gene amplification with an activating mutation of PIK3CA. Cancer Res 69:7357-65
Hu, Nan; Wang, Chaoyu; Ng, David et al. (2009) Genomic characterization of esophageal squamous cell carcinoma from a high-risk population in China. Cancer Res 69:5908-17
Yang, Howard H; Hu, Nan; Taylor, Philip R et al. (2008) Whole genome-wide association study using affymetrix SNP chip: a two-stage sequential selection method to identify genes that increase the risk of developing complex diseases. Methods Mol Med 141:23-35
Lee, Maxwell P; Dunn, Barbara K (2008) Influence of genetic inheritance on global epigenetic states and cancer risk prediction with DNA methylation signature: challenges in technology and data analysis. Nutr Rev 66 Suppl 1:S69-72
Ng, David; Hu, Nan; Hu, Ying et al. (2008) Replication of a genome-wide case-control study of esophageal squamous cell carcinoma. Int J Cancer 123:1610-5
Hu, Nan; Wang, Chaoyu; Hu, Ying et al. (2005) Genome-wide association study in esophageal cancer using GeneChip mapping 10K array. Cancer Res 65:2542-6
Lin, Wei; Yang, Howard H; Lee, Maxwell P (2005) Allelic variation in gene expression identified through computational analysis of the dbEST database. Genomics 86:518-27
Lee, Maxwell P; Howcroft, Kevin; Kotekar, Aparna et al. (2005) ATG deserts define a novel core promoter subclass. Genome Res 15:1189-97
Lee, Maxwell P (2005) Genome-wide analysis of allele-specific gene expression using oligo microarrays. Methods Mol Biol 311:39-47

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