This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-20-032. Compared to other ancestral groups, men of African ancestry (MAA) have the highest incidence and mortality of prostate cancer (Prostate cancer), with African men having the highest. Although socio-economic factors have been shown to contribute to this disparity, the sum of those factors fails to adequately explain the magnitude of the impact. Multiple studies have demonstrated that genetic/biologic differences in African American (AA) tumor biology contribute to Prostate cancer development and aggressiveness. Moreover, there is building evidence to support that the observed differences are population specific and form unique paths to cancer aggressiveness. Unfortunately, most contemporary evidence, regarding Prostate cancer in MAA, focus on AA men not African men. This lack of adequate representation greatly diminishes the ability to not only identify meaningful clinical interventions for this patient population but also the opportunity to investigate the shared genetic background of both groups for causal disease variants, overlaid by gene expression. Thus, this necessitates a greater emphasis on the need for a multi-omics approach to identifying clinical interventions that can help these underrepresented patient population. To more broadly understand the role of mutations and that lead to events such as DNA methylation in patients with African Ancestry, we performed whole exome sequencing of Nigerian Prostate cancer FFPE samples to determine the mutational landscape of men with prostate cancer in West Africa. Interestingly, we found that a number of novel mutations, however mutation signatures suggest that Nigerian Prostate tumors contain a substitution bias toward C>T and T>C transitions, thus increasing the possibilities for DNA methylation patterns in this population. Furthermore, since our lab for the past decade has demonstrated that Kaiso is a master regulator of multiple methylated genes expression, and that Kaiso is associated with suppressive immune microenvironment, we propose the following aims:
Specific Aim 1 - Perform DNA methylation profiling on Nigerian Prostate Cancer Patients;
and Specific Aim 2 Perform Multi-Spectral Imaging of Nigerian Prostate Cancer FFPE samples.
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-20-032. Compared to other ancestral groups, men of African ancestry (MAA) have the highest incidence and mortality of prostate cancer (Prostate cancer), with African men having the highest. To address this we are proposing to develop a multi-omics approach to identifying clinical interventions that can help these underrepresented patient population.
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