The Genomic Landscape of Papillary Renal Cell Carcinoma Arising in African American Patients
Abstract
Kidney cancer is a common and lethal disease in the United States, resulting in nearly 15,000 deaths annually, and almost 75,000 new cases are diagnosed annually. Nearly one in four patients with kidney cancer will die within five years of diagnosis, making this the most lethal cancer in the urinary system in humans. African Americans (AA) tend to develop kidney cancer at a higher rate than people of European descent, and AA patients diagnosed with kidney cancer appear to die from this disease at a much higher rate than other ethnicities. A subtype of kidney cancer is called papillary renal cell carcinoma (pRCC), which represents 10%-15% of kidney tumors. This variant of kidney cancer affects patients of African descent three times more commonly than other patients. Some data suggests that AA patients are more likely to die from pRCC whereas other data suggest otherwise. Previous studies have evaluated pRCC genes in search of altered genes that cause these tumors to grow and spread. Several genes appear to be responsible for the development of these tumors. Unfortunately, tumor samples from African American patients were only a very tiny fraction of the tumors evaluated in these studies. Consequently, it is not clear if these genetic changes seen in samples from predominantly white patients are consistently found in patients of African descent. Furthermore, there is no available data to indicate why AA subjects develop these tumors at such a higher rate than non-AA patients. In addition, other factors may contribute to the higher rate of pRCC in AA subjects such as obesity, hypertension, and renal failure. None of these has been evaluated from a gene evaluation approach in the available published studies. Our proposal is focused on identifying gene alterations and RNA expression differences in tumors obtained exclusively from AA patients. The first phase will be to obtain DNA from several different locations of each tumor as well as from normal kidney tissue. This DNA will be broadly evaluated for gene alterations, particularly changes that appear to be unique. This by itself will be an addition to the existing knowledge since this has not been done in a large cohort of pRCC tumors from AA patients. The second goal is to evaluate the amounts and types of RNA that are expressed in the tumors not only from known genes but also from DNA that does not translate into proteins. This evaluation will add to the existing knowledge in the medical literature. Ultimately, this new information will allow us to identify candidate genes that may be the genetic causes of these tumors and possibly explain why these tumors grow and spread. This new information will enable further research to find ways to stop these genes from eventually causing tumors to grow and spread.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110983
Entities
People
- Adam Metwalli
Organizations
- Howard University
- United States Army