Abstract

I have applied our high-throughput genomic/epigenomic technologies, such as high-density SNP arrays and next-generation sequencing (NGS) technology, to identifying genes that present as plausible candidates for contributing to breast cancer development. The genomic investigation has led to the identification of two putative oncogenes, IRX2 and TBL1XR1. Our research has provided direct experimental evidence supporting an oncogenic effect for TBL1XR1 and IRX2. Our epigenomic investigation has led to the identification of DNA methylation signatures that are selectively associated with clinical phenotypes such as lymph node involvement, histological grade, tumor size, and ER/PR/HER2 status. Our methylation signature recapitulates gene expression signature and can distinguish luminal versus non-luminal breast tumors. Furthermore, our methylation signature can provide information, beyond gene expression, to refine sub-classification of luminal breast tumors.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011253-03
Application #
8553065
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$556,263
Indirect Cost

  Institution

Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Lee, Maxwell P (2012) Allele-specific gene expression and epigenetic modifications and their application to understanding inheritance and cancer. Biochim Biophys Acta 1819:739-42
Su, Hua; Hu, Nan; Yang, Howard H et al. (2011) Global gene expression profiling and validation in esophageal squamous cell carcinoma and its association with clinical phenotypes. Clin Cancer Res 17:2955-66
Kadota, Mitsutaka; Yang, Howard H; Gomez, Bianca et al. (2010) Delineating genetic alterations for tumor progression in the MCF10A series of breast cancer cell lines. PLoS One 5:e9201
Hu, Nan; Clifford, Robert J; Yang, Howard H et al. (2010) Genome wide analysis of DNA copy number neutral loss of heterozygosity (CNNLOH) and its relation to gene expression in esophageal squamous cell carcinoma. BMC Genomics 11:576
Abnet, Christian C; Freedman, Neal D; Hu, Nan et al. (2010) A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat Genet 42:764-7
Yang, Howard H; Hu, Nan; Wang, Chaoyu et al. (2010) Influence of genetic background and tissue types on global DNA methylation patterns. PLoS One 5:e9355
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