The purpose of this application is to request NCCR SIG funding for a Transgenomic Wave dHPLC system for the newly formed Translational Research Laboratory in the Center for Clinical and Translational Research at the Dana-Farber Cancer Institute. This system will establish an essential platform for screening and detection of known and unknown mutations in archival and ongoing clinical trial patient tissue samples. The grant describes the capabilities of the Transgenomic Wave System and how the instrument would enhance the overall quality and efficiency of clinical and translational researchers' investigations and lead to tangible reduction in the suffering caused by the cancer scourge. ? ? The Translational Research Laboratory has as its mandate through the strategic plan of the DFCI to improve clinical trial science by providing clinical investigators with an interdisciplinary forum to share research ideas and issues, collaborative technical and scientific expertise, access to the latest technology, and resources to develop and validate new technologies to analyze relevant biological markers, surrogates and drug targets in patients. ? ? We have found the Transgenomic WAVE(r) System to be the most sensitive and accurate technology available for detection of genetic mutations and polymorphisms, and unlike gel-based systems the WAVE systems are fully automated, robust, versatile and cost effective. The WAVE System is more sensitive, faster and less expensive to operate than automated DNA sequencing or any of the traditional gel-based techniques, such as SSCP, TDGS, etc. Efficiency is increased and costs reduced because greater sensitivity allows for multiplexing and screening by dHPLC, and allows us to sequence only those samples that contain a mutation or SNP. ? ? The acquisition of this machine will help our clinicians/researchers narrow the gap between the great advances in the development of targeted drugs for cancer and our understanding of how, when, and who these drugs will help. A case in point is the development of epidermal growth factor receptor inhibitors. The remarkable benefits of these drugs in treating lung cancer were only fully understood and the use of the drug defined with an understanding that efficacy hinged on the presence of somatic mutations in the EGFR gene. ? ? ?
