National Cancer Institute, Research Contracts Branch, PSAS, 6120 Executive Blvd, EPS/Room 638, Bethesda, MD 20892-7227

B -- SPECIAL STUDIES AND ANALYSIS SOL RFQ-NCI-90134 DUE 090799 POC Cynthia Brown, Purchasing Agent, 301-402-4509, Todd Cole, Contracting Officer The National Cancer Institute (NCI), Division of Clinical Sciences (DCS), Cancer Prevention Studies Branch (CPSB) has plans to procure services from Thetagen, Inc., 600 Broadway Street, Suite 510, Seattle, WA 98122. The services entail obtaining analyzed data on DNA repair enzyme polymorphisms in DNA collected from lung cancer case and control case samples from the Yunnan Province in China. BACKGROUND: Lung cancer is the leading cause of death from malignant neoplasms in the United States and in many countries around the world. The Yunnan Province in southern China may provide some insight into this type of cancer. Yunnan has had a large, nonferrous-metals industry since 1883. The tin miners at YTC have extremely high rates of lung cancer. Those at high risk are defined as miners 40+ years old with 10+ years of underground mining and/or smelting experience. More than one percent per year of those at risk develop lung cancer each year. These extraordinary lung cancer rates result from combined exposure to radon arsenic, and tobacco smoking in the form of cigarettes and/or bamboo water pipe. Samples of sputum have been collected under studies for over twenty years; likewise, DNA has been isolated from blood specimens and stored for genetics and cancer association studies. In order to understand the role of genetic polymorphisms in the etiology of lung cancer, the CPSB now requires the analysis of DNA repair enzyme polymorphisms from some of the aforementioned DAN samples previously collected. The required services stem from earlier mass throughput developmental work and optimization of the ABI Prism 7700 genotyping techniques (TaqMan) with Thetagen. This novel approach, as described below, provided extremely accurate and reproducible results, with 100% concordance rates in all blinded control samples analyzed. Specifically, the Taqman technique is a novel allele discrimination assay based on an ABI Prism 7700 Sequence Detection System. The system detects base changes, mismatches and large deletion mutations. In this technique, allele discrimination involves 2 diagnostic TaqMan probes, each specific for one of the target alleles. Each probe is labeled on the 5' end with a reporter dye and on the 3' end with a quencher. Both probes are included in a single PCR based reaction where hybridization conditions are optimized to discriminate between matched and mismatched probes. Perfectly matched TaqMan probes are cleaved by the 5'-3' nuclease activity of Taq polymerase causing an increase of reporter signal. An increase in signal from one of the 2 reporter dyes indicates homozygosity at the allele, while increase in both reporter dyes indicate heterozygosity. Thetagen developed this approach for genotyping assays for DNA repair enzyme polymorphisms with mass throughput TaqMan techniques. This procedure can meet NCI's required needs of genotyping at least 1,000 samples in 24 hours with a 100% reproducibility rate. In addition, each genotype assay can be performed with as little as 1-5 nano-grams of genomic DNA. Thetagen is the only source known to the NCI Research that can meet the above throughput and reproducibility rates due to the novel approach using TaqMan DNA repair enzyme polymorphism genotyping. This is not a request for competitive quotation. However, if any interested party believes it can meet the above requirement, it may submit a statement of capabilities. The statement of capabilities and any other information furnished must be in writing and must contain material in sufficient detail to allow NCI to determine if the party can perform this requirement. Capability statements must be received in the contracting office by 3:00 p.m. EST on Sept. 7,1999. If you have any questions, please contact Cynthia Brown, Purchasing Agent, on (301) 402-4509. A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct acompetitive procurement. Posted 08/18/99 (W-SN369380). (0230)

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