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2025 Green Family Foundation – PCF Young Investigator Award

Decoding the Molecular Landscape of BRCA1/2-Associated Prostate Cancer: Insights from Single-Cell and Spatial Transcriptomics to Uncover Tumor Heterogeneity and Therapeutic Targets

Nabamita Boruah, PhD        
University of Pennsylvania     

Mentor: Kara Maxwell

Description:

  • BRCA1 and BRCA2 (BRCA1/2)are genes that function to repair damaged DNA, and hereditary alterations in these genes strongly increase risk for several cancer types including breast, ovarian, and prostate cancers. BRCA1 and BRCA2 gene alterations occur in 6.4% and 24.3%, respectively, in patients with prostate cancer. Notably, BRCA2 alterations are strongly linked to more aggressive disease phenotypes, earlier onset, and poorer survival outcomes. 
  • Prostate cancer is highly variable, both clinically and biologically, and identifying tumor-associated cellular phenotypes is critical for understanding disease progression. Importantly, African American men experience disproportionately high rates of aggressive prostate cancer and poorer survival outcomes, likely due to a combination of genetic and social factors. Understanding the molecular and cellular mechanisms behind these disparities is essential for improving outcomes in this underserved population. 
  • Dr. Nabamita Boruah’s project will investigate the cellular heterogeneity in BRCA1/2-associated prostate cancer, with a particular emphasis on African American patients.
  • Her team will investigate how loss-of-function mutations in BRCA1/2 influence prostate cancer biology at the cellular level, by comparing genomic alterations and gene expression profiles between hereditary BRCA1/2carriers and non-carriers. 
  • Additionally, how BRCA1/2 mutations impact spatial organization and gene expression patterns within prostate tumors will be investigated by comparing prostate tumor samples from hereditary BRCA1/2 carriers and non-carriers.
  • If successful, this project will uncover the molecular and cellular underpinnings of prostate cancer linked to BRCA1/2 mutations, particularly within underrepresented Black populations. 

What this means to patients: Hereditary alterations in the BRCA1 and BRCA2 genes are associated with an estimated lifetime risk for prostate cancer of 20% and 40%, respectively. These alterations are also more prevalent in African ancestry individuals and are associated with earlier diagnosis and more aggressive disease, but may also render patients eligible for PARP inhibitors therapy. Dr. Boruah’s project will define the genomic, molecular, and spatial differences of prostate cancer with vs. without BRCA1/2 alterations. This research has the potential to transform our understanding of prostate cancer biology, improve clinical practices, and guide targeted prevention strategies, ultimately enhancing patient outcomes and reducing disparities in prostate cancer care.