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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA183027-01
Application #
8639619
Study Section
Special Emphasis Panel (ZCA1-SRLB-R (O1))
Program Officer
Henderson, Lori A
Project Start
2014-02-12
Project End
2017-01-31
Budget Start
2014-02-12
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$416,880
Indirect Cost
$148,790
Name
University of Michigan Ann Arbor
Department
Pathology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109