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Validation and Interrogation of Differentially Expressed and Alternatively Spliced Genes in African-American Prostate Cancer

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Technical Report,30 Sep 2014,29 Sep 2015

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Duke University Durham United States

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These studies address the urgent need to elucidate the molecular mechanisms underlying the more aggressive prostate cancer biology in African American AA men. Specifically, our objectives are to 1 expand our sample cohort and delineate the relationship between geneticepigeneticpost-transcriptional factors in AA prostate cancer and Gleason grade and 2 manipulate splicing using novel splice-switching oligonucleotides SSOs and determine functional outcomes. Toward these objectives, we have opened our GENomics of Cancer DisparitiEs Study to obtain AA and white prostate cancer blood and tissue specimens. For all tissue specimens collected, we have screened for tumor content, determined Gleason grade, isolated DNA and RNA and annotated. In addition, we have developed SSOs to manipulate PIK3CD alternative splicing, to correct aberrant splicing leading to production ofAR-V7 and to drive production of inhibitory androgen receptor and epidermal growth factor receptor isoforms. Ultimately, this study will establish the geneticepigeneticpost-transcriptional differences between AA and white prostate cancer and their relevance to tumor biology, which will pave the way toward identification of novel biomarkers andor molecular targets for precision medicine that will reduce prostate cancer health disparities for AAs and improve outcomes for men of all races with aggressive disease.

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