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The Molecular Profile of Prostate Tumors in African-Amer

$0Z01FY2006BCNIH

Basic Sciences

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Abstract

We investigated the gene expression profiles of 69 primary prostate tumors from prostatectomy patients obtained from the NCI Prostate Tissue Network (CPCTR) and the University of Maryland. The tumors are from 33 African-American and 36 Caucasians, and have a similar stage and Gleason score distribution in the two groups. All cases had a diagnosis of adenocarcinoma and did not receive radiation, chemotherapy, hormone therapy, or immunotherapy, prior to the prostatectomy. Additional information on pathological stage, Gleason score, percentage of tumor in the specimen, size of tumor, presence of extraprostatic extension (perineural, seminal, or angiolymphatic), prostate-specific antigen (PSA) status at diagnosis, biochemical recurrence status, smoking status (current, former, or never smoker), was also obtained.We completed the assessment of the microRNA and mRNA expression profiles in whole tissue samples. We are currently using laser capture microdissection (LCM) to collect enriched tumor epithelium and the adjacent stroma from 30 to 40 tumors. The microdissected samples will give us more detailed information on the specific gene expression profiles of cancer cells and stromal cells. Preliminary analysis shows gene expression differences for mRNA and microRNA by race/ethnicity. The differently expressed genes cluster in distinct pathways that are partly in common with the high versus low Gleason score and tumor versus normal contrasts. We are verifying the observations in an independent sample set in collaboration with James Goedert, NCI/DCEG. We will employ more analysis tools to pinpoint the gene expression differences between African-Americans and Caucasians to pathways that are most crucial in prostate cancer progression. We will also investigate whether certain gene expression differences are related to common genetic variations in these two race/ethnic groups.

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