Abstract A075: Characterizing novel aggressive prostate cancer subtypes associated with loss of chromosomes 8p and 16q

Abstract

Abstract Roughly 15% of the 268,490 men newly diagnosed with prostate cancer (PCa) will die from the disease. Pinpointing the drivers of aggressive PCa is the first step to improve patient outcomes. Correlative analyses have linked genetic aberrations, including copy number alterations due to loss of large genomic regions, to poor prostate cancer prognosis. Many groups have connected the loss of chromosome 8p and 16q to aggressive PCa, yet the genes on these regions responsible for aggressive phenotypes are unknown. Mining TCGA data, we identified minimum consensus deletions and associated gene expression with disease recurrence to nominate 48 genes on 8p and 58 genes on 16q for further study. We designed a pooled double knockout library to test all pairwise gene combinations of the nominated 8p-16q genes. Gene pairs will be targeted by 16 paired crRNA cassettes consisting of four crRNAs per gene and paired in all combinations. This library will be combined with stably expressing Cas12a prostate epithelial cell lines to screen for gene combinations that drive excessive cell proliferation. This will help pinpoint specific PCa tumor suppressors in combined 8p and 16q loss. Citation Format: Gabriel A. Yette, James C. Costello, Scott D. Cramer. Characterizing novel aggressive prostate cancer subtypes associated with loss of chromosomes 8p and 16q [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A075.