Prostate Cancer Research
Progress Report: Mark Pomerantz, MD
Investigator: Mark Pomerantz, MD – Instructor in Medicine, Dana-Farber Cancer Institute, Harvard Medical School
Functional and Clinical Annotation of Inherited Prostate Cancer Risk Loci
Since the completion of the human genome project in 2003, there have been numerous reports in cancer studies, especially in prostate cancer, showing how small genetic alterations, called single nucleotide polymorphisms (SNPs) confer an increased risk of cancer. SNPs occur when one letter in the DNA code is changed to another letter. There are approximately 3 billion letters in the human genome. To date, 35 SNPs have been discovered that predict a higher risk for prostate cancer. However, the clinical utility of these findings and the significance to individuals has been elusive.
Understanding how these SNPs cause cancer is the goal of Dr. Pomerantz’s research. In the second year of his three year PCF Young Investigator Award, he reported that certain SNPs interact and affect gene expression of cancer-causing genes 1,000s of letters away in the genome. In baseball parlance, imagine an infielder in Los Angeles fielding a ground ball and throwing out a runner at first base in Chicago. Dr. Pomerantz’s findings are unique and show how genetic events occurring great distances away in the genome might combine to cause prostate cancer.
Additionally, Dr. Pomerantz reported that SNPs which confer increased risk for prostate cancer are functionally specific to prostate cells and are not active in breast and colon cells. This demonstrates that these SNPs are cell-type dependent and that understanding their function will require disease-specific analysis.
Dr. Pomerantz has made significant progress during the second year of his Young Investigator research project. His work has generated actionable results that begin to define the functional causes of inherited prostate cancer risk at the fine genetic level. These findings may lead to the discovery of new classes of therapeutics that target the harmful activity of genetic alterations in inherited prostate cancer.