An Assay System for Cancer Gene Discovery

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DESCRIPTION (provided by applicant): The aim of this project is to develop an innovative, highly efficient assay for detecting genes that may be functionally important in cancer. There are a number of challenges to detecting such genes, including the extensive mutation and rearrangement of the cancer genome; the variety of molecular mechanisms which can go awry, leading to extensive molecular variation between cancers; and the heterogeneity of cancer samples, which tend to include a mixture of cell types, both normal and abnormal. Our strategy for detecting cancer causing genes is to apply microarray concepts to enable a high-throughput genome-wide screening approach that will help overcome some of the challenges due to molecular and cellular heterogeneity. In the first phase of the project, we intend to develop a simple model system for assay development by constructing plasmid clones and using synthetic oligonucleotides specific for a small number of genes. In Phase II, we will expand the assay system to include a large set of genes, and we will validate the assay system using actual cancer samples and controls. We expect that, once developed, our approach will allow many samples to be screened at a high resolution, rapidly, reliably and cost- effectively. Our approach may enable the discovery of new genes that play an important role in cancer. Some genes that help transform normal cells into cancerous ones have proven to be good targets for the development of more effective cancer drugs. However, much remains to be discovered about such genes and the mechanisms by which they act. This proposal is aimed at developing a powerful and efficient new way to find important cancer genes, which may lead to a better understanding of the disease and improved tests and treatments.