Landscape of Mutations in 500 Prostate Cancer Whole Genomes
Abstract
The purpose of this study is to examine the genetics of prostate cancer tumors to gain more in-depth understanding of the factors that contribute to emergence of this disease and those that transform a non-aggressive disease into one that spreads to other organs of the body and is often fatal. The main aim of this study is to uncover signatures from the tumor’s DNA, which are able to classify newly diagnosed patients into those whose tumors grow slowly, and thus have a better prognosis, and those who will develop an aggressive and metastatic disease. This will allow more effective administration of treatment to patients; those with better prognosis can remain under active surveillance without receiving unnecessary treatments, such as radiotherapy or radical prostatectomy, while those with worse prognosis will be treated immediately in a more comprehensive manner. This will lead to a better quality of life for men who continue to have a non-aggressive disease and a higher chance of survival for men with aggressive disease. During the 2 years of the proposed project, investigation of the available dataset, consisting of 500 prostate cancer patients, will be conducted, and potential informative signatures will be tested for accuracy on a separate cohort of patient samples that are projected to become available in the near future. The subsequent step will be to test the efficacy of the findings in a clinical setting. Dr. Boutros, the Principal Investigator’s (PI) mentor, and his collaborators have extensive experience in translating such knowledge into the clinic and will be instrumental in advancing the practical applications of the findings. The PI’s career goal is to establish an independent laboratory where she is able to conduct research on prostate cancer according to her vision and alongside her colleagues in the field. Her research goal is to apply data science analytics to the study of the large datasets that are generated from prostate cancers. In the past few years, we have seen a significant increase in the number of patients who have their tumor and blood samples sequenced. This is the direct result of advances in technology, plummeting costs, and anticipation of the effects of personalized medicine on cancer care and outcome. The available molecular data are only expected to continue to increase in volume; therefore, more sophisticated algorithms are necessary to analyze and interpret them. The PI’s training in genetics, computer science, and bioinformatics makes her a qualified candidate for conducting such large-scale computational experiments on prostate cancer. Through fulfilling the aims of this proposed project, the PI will gain further expertise in analysis of prostate cancer cohorts, as well as insight into the strengths and limitations of such studies and how to best overcome them. The results of this project will be disseminated publicly through open-source publications and conference presentations. As a result, the PI will have opportunities to more broadly interact with other scientists in the field and learn and collaborate with them, thus preparing her for a successful career as an independent investigator. The PI’s mentor, Dr. Paul Boutros, is a world-renowned scientist, whose work on prostate cancer has been published in several high-impact journals, thus contributing significantly to our understating of this malignancy. He is a core leader of the Canadian Prostate Cancer Genome Network (CPC-GENE), the largest prostate cancer study in the world, and is also a core member of international prostate cancer studies such as The Cancer Genome Atlas project and the International Cancer Genome Consortium. He has mentored over 120 undergraduate and graduate students, as well as medical and post-doctoral fellows, and has been recognized for his dedication to the training of future scientists by the University of Toronto Early Career Excellence in Graduate Teaching and Mentorship. H
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810305
Entities
People
- Katayoon Kasaian
Organizations
- Ontario Institute for Cancer Research
- United States Army