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Stroma Based Prognosticators Incorporating Differences between African and European Americans

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University of California Irvine United States

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Our objective is to identify and validate RNA prognosticators for prostate cancer in European Americans EAand African Americans AA, and port these to DNA methylation and protein-based prognosticators, where possible. The unique aspects of this project are that it uses tumor-adjacent stroma as a source of markers, and uses standard Formalin-fixed Paraffin-embedded FFPE tissue, which is a challenge for molecular biology. In the first year, we profiled RNA by multiplex array cards and found that only half the samples were of adequate quality. Even fewer DNA samples from the same patients were amenable to bisulfite sequencing of more than a few genes. Exploiting the recent three-fold reduction in the cost of sequencing per read, we developed oligo capture sequencing methods to extract global RNA expression data, and antibody methods to capture genome-wide DNA methylation data. These protocols work on samples over almost the entire range of quality and yield, which would otherwise be lost to the study. Many of these samples are all the more precious owing to longer follow-up including samples from AA patients. We used Gleason Score, chemical relapse status, and approximate age, to match patients. We have now obtained comprehensive expression data from 18 AA, and 27 matched EA, and genome-wide methylation data from 13 and 7 of the same patients. Awaiting analysis are all the required additional pairs of AA and EA patients.

Descriptive Note:

Technical Report,30 Sep 2016,29 Sep 2017



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Approved For Public Release;

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