Race-related Alternative Splicing: Novel Targets in Prostate Cancer (PCaP splicing)

Duke University

Status: Completed

Conditions: Prostate Cancer

Treatments: Other: No interventions - retrospective data collection

Study type: Observational

Funder types: Other

Identifiers

NCT03424213

Pro00091092

Details and patient eligibility

About

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.

Enrollment: 169 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

169 participants in 6 patient groups

white low aggressive

Description:

low aggressive = Gleason score \< 7 and stage cT1-cT2 and PSA \< 10 ng/ml

Treatment:

Other: No interventions - retrospective data collection

white high aggressive

Description:

high aggressive = Gleason score ≥ 8 or PSA \> 20 ng/ml or Gleason score = 7 and stage cT3-cT4

Treatment:

Other: No interventions - retrospective data collection

white intermediate aggressive

Description:

intermediate aggressive = all other cases

Treatment:

Other: No interventions - retrospective data collection

AA low aggressive

Description:

low aggressive = Gleason score \< 7 and stage cT1-cT2 and PSA \< 10 ng/ml

Treatment:

Other: No interventions - retrospective data collection

AA high aggressive

Description:

high aggressive = Gleason score ≥ 8 or PSA \> 20 ng/ml or Gleason score = 7 and stage cT3-cT4

Treatment:

Other: No interventions - retrospective data collection

AA intermediate aggressive

Description:

intermediate aggressive = all other cases

Treatment:

Other: No interventions - retrospective data collection