103 Proteomic Approaches within the NCI Early Detection Research Network for the Discovery and Identification of Cancer Biomarkers MUKESH VERMA, a GEORGE L. WRIGHT, JR., b SAMIR M. HANASH, c RASHMI GOPAL-SRIVASTAVA, d AND SUDHIR SRIVASTAVA a a Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland, USA b Department of Microbiology and Molecular Cell Biology and Virginia Prostate Center, Eastern Virginia Medical School, Norfolk, Virginia, USA c Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA d Division of Extramural Activities, National Cancer Institute, Bethesda, Maryland, USA ABSTRACT: In the postgenome era, proteomics provides a powerful approach for the analysis of normal and transformed cell functions, for the identification of disease-specific targets, and for uncovering novel endpoints for the evalua- tion of chemoprevention agents and drug toxicity. Unfortunately, the genomic information that has greatly expounded the genetic basis of cancer does not allow an accurate prediction of what is actually occurring at the protein level within a given cell type at any given time. The gene expression program of a given cell is affected by numerous factors in the in vivo environment resulting from tissue complexity and organ system orchestration, with cells acting in concert with each other and responding to changes in their microenvironment. Repositories of genomic information can be considered master “inventory lists” of genes and their maps, which need to be supplemented with protein- derived information. The National Cancer Institute’s Early Detection Research Network is employing proteomics, or “protein walking”, in the discovery and evaluation of biomarkers for cancer detection and for the identification of high-risk subjects. Armed with microdissection techniques, including the use of Laser Capture Microdissection (LCM) to procure pure populations of cells directly from human tissue, the Network is facilitating the development of tech- nologies that can overcome the problem of tissue heterogeneity and address the need to identify markers in easily accessible biological fluids. Proteomic approaches complement plasma-based assays of circulating DNA for cancer detection and risk assessment. LCM, coupled with downstream proteomics applications, such as two-dimensional polyacrylamide gel electrophoresis and SELDI (surface enhanced laser desorption ionization) separation followed by mass spectrometry (MS) analysis, may greatly facilitate the characterization and identification of protein expression changes that track normal and disease phenotypes. We highlight recent work from Network investigators to demon- Address for correspondence: Sudhir Srivastava, Ph.D., M.P.H., Chief, Cancer Biomarkers Research Group, Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, 6130 Executive Boulevard, EPN-330F, Rockville, MD 20852-7346. Voice: 301-435- 1594; fax: 301-402-8990. ss1a@nih.gov