Abstract PR01: Distinct genomic alterations in prostate cancer of African American men

Abstract

Background: Emerging observations highlight distinct biology of prostate cancer (CaP) among men of different ethnicities and races. Studies including reports from our institute have demonstrated remarkable ethnic/racial differences in the frequency of ERG oncogenic activation, one of the most common and widely studied CaP driver genes. Similarly, deletion of the PTEN tumor suppressor gene, an established cancer driver gene alteration, was shown to be more prevalent among men of European ancestry. We have reported the cumulative analyses of 435 patients (whole-genome sequencing [WGS]: 14, FISH evaluations: 101, SNP array: 320) comparing CaP genomes of African American and Caucasian American patients. An AA CaP genome associated minimum deletion site on 3q13.31 was identified by WGS and mapped to the Limbic System-Associated Membrane Protein (LSAMP) gene locus using the TCGA SNP array data of 44 AA and 260 CA tumors. Further, we also noted the AA CaP genome association of the Chromodomain Helicase DNA Binding Protein 1(CHD1) gene deletion. Methods: The frequency and prognostic associations of LSAMP, CHD1, and PTEN deletions was evaluated by FISH analyses in prostate tumor tissue microarray (TMA) with up to 20 years of follow-up. The TMA represented normal and tumor foci (1000+ cores) sampled by 2-3 cores including the spectrum of cell morphology and tumor pathology in matched cohort of 42 AA and 59 CA patients. ERG was evaluated in the same TMA by immunohistochemistry. Evaluation of ERG was extended to the assessment of whole mounted prostate sections of 336 AA and 594 CA patients from the equal-access military health care system, in which disparities in socioeconomic status, health awareness, and physical activity are minimized. Results: AA CaP genome-associated recurrent deletions of LSAMP (26% AA vs. 7% CA, p=0.006) and CHD1 (29% AA vs. 10% CA p=0.017) genes were identified. AA CaP patients harboring these genomic deletions in their CaP showed significantly higher risk of rapid disease progression as measured by biochemical recurrence. Consistent with previous reports, we noted significantly lower frequency of PTEN deletions (15% AA vs. 63% CA) and ERG expression (26% AA vs. 64%) in prostate cancers among AA men. In-depth evaluation of ERG frequencies in the context of multifocal disease provided definitive evidence for the difference in the frequency of ERG between AA (23%) and CA (49%) patients from the equal-access military health care system. Conclusions: Our study underscores that the biology of CaP has to be taken into consideration when new diagnostic and prognostic markers and therapeutic approaches are being developed in order to realize the true potential of precision medicine for all cancer patients. Note: This abstract was not presented at the conference. Citation Format: Albert Dobi, Gyorgy Petrovics, Hua Li, Denise Young, Yongmei Chen, Jacob Kagan, Sudhir Srivastava, Reinhard Ebner, Inger L. Rosner, Jennifer Cullen, Matthew L. Freedman, Isabell A. Sesterhenn, Zoltan Szallasi, Shiv Srivastava. Distinct genomic alterations in prostate cancer of African American men [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr PR01.