The diagnosis of localized prostate has traditionally been performed with transrectal ultrasound (TRUS) guided biopsy and men found to have localized, organ-confined prostate cancer are conventionally managed with surgical removal of the prostate, radiation therapy or active surveillance. Until recently, limitations of prostate imaging and tumor assessment have greatly limited our ability to accurately assess the genetic and metabolic abnormalities associated with an individual's localized prostate cancer in order to guide subsequent clinical management. In addition, understanding the genetic and metabolic basis of prostate cancer has the potential to provide the foundation for the development of effective forms of therapy for this disease. This application attempts to marry the advanced MRI and metabolic imaging of prostate cancer developed at the NIH with the integrative clinical sequencing approaches employed by the Michigan Center for Translational Pathology (MCTP). Given this the Aims are as follows:
Aim 1, Enroll patients with known or suspicious for prostate cancer in the NIH MRI/metabolic imaging program.
Aim 2, Whole exome and transcriptome sequencing analysis of 60 patients identified with clinically localized prostate cancer from frozen biopsy material obtained in Aim 1. We will carry out integrative sequencing that involves whole exome sequencing of the tumor/normal, and paired-end transcriptome and exome-capture transcriptome sequencing. By carrying out these analyses, we propose that we would be capturing the universe of actionable and informative mutations a patient might harbor in their tumor. These mutations include somatic nucleic acid substitutions, small indels, gene fusions/translocations, amplifications/deletions, and outlier gene expression.
Aim 3, Integrative analysis of histopathology, molecular imaging, metabolism, mutational landscape and gene expression alterations of biopsy material from this clinical trial. The biopsies will undergo pathologic analysis as well as comprehensive molecular profiling in order to make associations with matched multiparametric MRI, C13 hyperpolarized imaging and pathology with the intended goal of determining the genetic basis of indolent versus aggressive cancers.
Prostate cancer is the leading cause of cancer and the second most common cause of cancer-related death in men. By combining advanced MRI and metabolic imaging with genomic sequencing, we hope to better understand what makes some prostate cancers aggressive and others indolent.
