Race-related Alternative Splicing: Novel Targets in Prostate Cancer
Status: | Recruiting |
---|---|
Conditions: | Prostate Cancer, Cancer |
Therapuetic Areas: | Oncology |
Healthy: | No |
Age Range: | 18 - Any |
Updated: | 1/31/2019 |
Start Date: | January 30, 2018 |
End Date: | January 2020 |
Contact: | Jennifer Freedman, PhD |
Email: | Jennifer.Freedman@duke.edu |
Phone: | 919-684-6354 |
Data from evaluating prostate cancer (PCa) biopsy tissue from AA and white patients has led
to the discovery of alternative splicing as a novel molecular mechanism underlying more
aggressive PCa in AA men. Coded archival radical prostatectomy tissue specimens and annotated
clinical data, questionnaire data, and ancestral genotyping data will be obtained from the
racially diverse and federally funded North Carolina-Louisiana PCa Project (NC-LA PCaP). We
will use 33 tissue specimens from each of the following 6 groups (n=198 total): white low
aggressive, white intermediate aggressive, white high aggressive, AA low aggressive, AA
intermediate aggressive and AA high aggressive. The aforementioned tissues will first be
screened for tumor content and Gleason grade by a genitourinary pathologist. To identify
race-related splice variants, RNA will be isolated for targeted sequencing of prioritized
race-related alternatively spliced genes using the NimbleGen SeqCap Target Enrichment, SeqCap
RNA System to capture regions of interest and the Illumina HiSeq sequencing platform to
sequence these regions at a depth and coverage sufficient to accurately call alternative
splicing events.
to the discovery of alternative splicing as a novel molecular mechanism underlying more
aggressive PCa in AA men. Coded archival radical prostatectomy tissue specimens and annotated
clinical data, questionnaire data, and ancestral genotyping data will be obtained from the
racially diverse and federally funded North Carolina-Louisiana PCa Project (NC-LA PCaP). We
will use 33 tissue specimens from each of the following 6 groups (n=198 total): white low
aggressive, white intermediate aggressive, white high aggressive, AA low aggressive, AA
intermediate aggressive and AA high aggressive. The aforementioned tissues will first be
screened for tumor content and Gleason grade by a genitourinary pathologist. To identify
race-related splice variants, RNA will be isolated for targeted sequencing of prioritized
race-related alternatively spliced genes using the NimbleGen SeqCap Target Enrichment, SeqCap
RNA System to capture regions of interest and the Illumina HiSeq sequencing platform to
sequence these regions at a depth and coverage sufficient to accurately call alternative
splicing events.
Inclusion Criteria:
1. Confirmed diagnosis of prostate cancer.
2. Self-reported race of AA or white.
3. Availability of five unstained slides per radical prostatectomy specimen and an
associated Hematoxylin and Eosin stained slide for each radical prostatectomy specimen
from NC-LA PCaP.
4. Classification of prostate cancer of low, intermediate or high aggressiveness, as
defined by NC-LA PCaP.
Exclusion Criteria:
1. Obtained radical prostatectomy tissue is inadequate for RNA analysis and/or is not
positive for adenocarcinoma of the prostate of low, intermediate or high aggressiveness.
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