Race-related Alternative Splicing: Novel Targets in Prostate Cancer

Study Overview
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Brief Summary
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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.

Official Title
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Race-related Alternative Splicing: Novel Targets in Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Other: No interventions - retrospective data collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of prostate cancer. Self-reported race of AA or white. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| white low aggressive<br>low aggressive = Gleason score < 7 and stage cT1-cT2 and PSA < 10 ng/ml | Other: No interventions - retrospective data collection<br>* No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data<br>|
| white high aggressive<br>high aggressive = Gleason score ≥ 8 or PSA > 20 ng/ml or Gleason score = 7 and stage cT3-cT4 | Other: No interventions - retrospective data collection<br>* No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data<br>|
| white intermediate aggressive<br>intermediate aggressive = all other cases | Other: No interventions - retrospective data collection<br>* No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data<br>|
| AA low aggressive<br>low aggressive = Gleason score < 7 and stage cT1-cT2 and PSA < 10 ng/ml | Other: No interventions - retrospective data collection<br>* No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data<br>|
| AA high aggressive<br>high aggressive = Gleason score ≥ 8 or PSA > 20 ng/ml or Gleason score = 7 and stage cT3-cT4 | Other: No interventions - retrospective data collection<br>* No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data<br>|
| AA intermediate aggressive<br>intermediate aggressive = all other cases | Other: No interventions - retrospective data collection<br>* No new patients will be consented to this study. Only retrospective data will be collected on prostatectomy specimens and correlated with health data<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of candidate race-related splice variants in localized prostate cancer of varying degrees of aggressiveness |  | at the time of analysis |