Validation and Interrogation of Differentially Expressed and Alternatively Spliced Genes in African-American Prostate Cancer
Technical Report,30 Sep 2015,29 Sep 2016
DUKE UNIV DURHAM NC 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 geneticepigeneticposttranscriptional 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 designed and synthesized SSOs to manipulate PIK3CD alternative splicing, with SSOs targeting the exon 23junction or a putative enhancer to produce the AA PIK3CD variant and targeting a putative repressor to produce the white PIK3CD variant.
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