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

A -- DEVELOP A DNA SEQUENCING METHOD TO ANALYZE A POLYMORPHISM IN THE ANDROGEN RECEPTOR SOL RFQ-90035-NV DUE 012799 POC Debbie Moore, Purchasing Agent 301-402-4509, Todd Cole, Contracting Officer 301-402-4509 The Medicine Branch (MB), Division of Clinical Sciences (DCS), National Cancer Institute (NCI) plans to procure the research services of Jing Jie Yu, M.D., 6000 42nd Ave., Apt 210, Hyattsville, MD 20781. The NCI is currently studying differences in the androgen receptor between individuals. Within one region of the androgen receptor, the repeat length has been shown to vary between individuals. This polymorphism has recently been linked to a prostate cancer risk. In a Physician Health Study out of Boston, a comparison was made between 368 men with prostate cancer and 368 age-matched controls. From the study, men with high grade and/or high stage prostate cancer had statistically significant higher proportion of short CAG repeats. An inverse relationship between CAG repeat length and cancer progression was identified. The study, although preliminary, appeared to be the first link to a specific germline genomic polymorphism and prostate cancer risk. This study may lead to the ability of stratifying men according to prostate cancer risk by a simple genomic test that could potentially alter current approaches to prostate cancer screening and/or prevention efforts. The Medicine Branch has developed and validated a method for quantifying the CAG repeat length from frozen serum, and patients enrolled in the Prostate Cancer Prevention Trial (conducted by NCI's Division of Chemoprevention and Cancer Control) will provide an ideal population for the analysis. The NCI requires a leading scientist on trinucleotide repeat in the androgen receptor to finalize aforementioned studies. To accomplish the study objectives herein, NCI requires the services of Jing Jie Yu, M.D., a skilled molecular biologist, who possesses extensive experience with the latest cancer genetics research technologies, particularly a technique for automated DNA sequencing which she shall use to assess the importance of this trinucleotide repeat in the androgen receptor. This technique involves nested PCR, followed by bacterial transfection for a clonal analysis. The extracted DNA is sequenced using a Perkin Elmer ABI Prism Automated Sequencer, similar to the one used in the Medicine Branch. Dr. Yu has optimized the conditions of this method in order to increase the yield of interpretable DNA sequences. She was involved in the above studies through a previous purchase order. Her expertise is needed to perform the final phases. She successfully generated solid data on the initial 40 samples from patients with prostate cancer to assess the relationship between CAG repeat numbers in the androgen receptor and the risk of prostate cancer. Dr. Yu has established and led many molecular and cellular biology assays, including: RT-PCR, SSCP, Southern blotting, northern blotting, and western blotting. These assays have been directed at several genes, including nucleotide excision repair genes ERCC1, XPA, XPB, XPD, XPF, XPG, and CSB, tumor suppressor gene p53, and cell cycle gene p16. Dr. Yu's work has resulted in a number of important publications that have appeared in peer-reviewed journals. Furthermore, Dr. Yu is proficient in performing DNA sequencing analysis using both the conventional isotopic-labeling method and the advanced fluorescent-dye technique. Of note, she discovered a previously indescribable ERCC1 nucleotide polymorphism (Mutation Research Genomics, 1997) that has been added to GenBank (accession #AF001925). Dr. Yu has investigated alternative splicing of ERCC1 mRNA and protein and cisplatin-DNA adduct repair in human cancer, which is of substantial importance in the measurement of ERCC1 as a possible marker for drug resistance to DNA damaging agents. Dr. Yu is trained in advanced techniques including: Advanced Methods DNA Sequencing; Concepts in Molecular Biology; Current Topics in Genome Analysis; Polymerase Chain Reaction & Molecular Hybridization Technology; Cancer Prevention & Control. Dr. Yu, a leading expert in cancer molecular biology/DNA sequencing is the only known source who can meet the requirements due to her vast experience, technical expertise, and training. If any interested party believes he/she can perform the above work and has significant experience in the above areas, he/she may submit a statement of capabilities. The statement of capabilities and any information furnished must be in writing and contain material in sufficient detail to allow the NCI to determine if the party can perform this requirement. Capability statements must be received in the contracting office by 1:00p.m. EST, on January 27, 1999. If you have any questions, please contact Debbie Moore, Purchasing Agent, at (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 a competitive procurement. Posted 01/11/99 (W-SN286693). (0011)

Loren Data Corp. http://www.ld.com (SYN# 0004 19990113\A-0004.SOL)