""""""""One of the major missions of NCI is to utilize the knowledge emanating from molecular biology to develop improved methods for risk analysis, diagnosis, and prognosis of cancer. Structure function studies of the proteins encoded by cancer-associated genes lead to new targets for intervention and therapeutic strategies. A dedicated service laboratory did not currently exist to assist with the pilot development of a new molecular marker from discovery to pilot clinical validation, particularly for solid tumor tissue specimens. Dr. Zhaung has established a Genetics Microanalysis Microdissection Unit. Dr Zhaung1s laboratory has incorporated the latest techniques in microdissection, cytogenetics, and image analysis. His ongoing work interfaces with flow cytometery, immunohistochemistry, and in situ hybridization functions already existing in the Laboratory. An important role for Dr. Zhaung is to provide applied research and development support for the new Cytogenetics service facility. He will coordinate and assist as needed to insure that the laboratory will be Accredited and CAP inspected. Dr. David Krizman manages a unit to support the development of cDNA libraries and high throughput microarray analysis to support the Cancer Genome Anatomy Project.The long term aim of the Cancer Genome Anatomy Project (CGAP) is utilize index sets of expressed genes to establish gene expression patterns for normal, precancerous, and malignant cells. These """"""""""""""""molecular profiles"""""""""""""""" will then be correlated with diagnosis, prognosis, and response to treatment. To initiate the CGAP, NCI has chosen five demonstration projects aimed at the development of an index set of expressed genes for breast, prostate, ovarian, lung and colon cancer progression stages. Analysis of each index set requires two distinct sequencing initiatives. The first phase is """"""""""""""""single pass"""""""""""""""" sequencing that includes the identification and sequencing of random cDNA clones, assessment of the quality of the libraries used to generate those sequences, and selection of specific cDNA clones as targets for further analysis. The second phase is full-length sequencing with a minimum 4-fold coverage of the targeted cDNA clones. The final full length clones will be incorporated into a growing collection of hybridization probes useful for a wide range of applications. One important application will be the development of a reference array of probes on chips or other media. The reference array will be used to compare the expression pattern of microdissected tissue samples from each neoplastic stage. The project has so far resulted in the production of more than 50 cDNA libraries. Successful adaption of microhybridization technology to microdissected cells, before and after PCR amplification, has been achieved.""""""""
