Grant: Catalyst Grant: Invention and High-Risk, High-Benefit Research

Fusion of two unrelated normal genes is a special genetic aberration associated with many human cancers. Over 400 unique fusion genes have been identified in human cancers, among which many of them exhibit specificity to certain cancer types or subtypes. Prostate cancer is the most common malignancy and the third leading cause of cancer death in men in Canada. The first fusion genes were not discovered in prostate cancer until 3 years ago, which involved fusion of an androgen-regulated gene with an oncogene. 18 different fusion genes have been identified since then, accounting for ~ 40% of overall prostate cancer cases. These fusion events are very specific to prostate cancer and offer great potential for noninvasive detection of exfoliated prostate tumor cells in bodily fluids. We propose that the reported fusion genes likely represent the "tip of the iceberg" in prostate and other human cancers, and that many novel fusion genes are yet to be unraveled. Thus, both common and low-prevalent fusion genes together represent a new class of noninvasive biomarkers that are associated with a broad spectrum of clinical tumors. The objectives of this proposal are: 1) to develop novel method for discovery and noninvasive detection of tumor-specific fusion genes, 2) to use the new method for noninvasive detection of all known fusion genes in prostate cancer, 3) to discover novel fusion genes associated with prostate cancer, and 4) to develop a powerful system for early screening and diagnosis of a broad-spectrum of human cancers. The proposed invention will have major impacts on technical innovation and new biomarker development in prostate and other human cancers. A high throughput platform will provide a powerful tool for discovery of novel fusion gene markers in prostate and other cancer. Meanwhile, a noninvasive, DNA chip-based fusion test will have immediate clinical applications in early screening and diagnosis of a broad spectrum of human cancers.