Abstract 781: DNA methylation patterns between aggressive and indolent prostate tumors from Puerto Rican men

Abstract

Abstract Background: In 2020, approximately 191,930 new prostate cancer (PCa) cases and 33,330 deaths are estimated in the US only. Hispanic/Latinos (H/L) are the second largest racial/ethnic group in the US. A previous study reported that prostate cancer-specific mortality rate among Puerto Rican men with prostate cancer is higher than ones of non-Hispanic Whites and non-Hispanic Blacks. The aims of this study are to: (1) assess the methylation patterns between aggressive and indolent PCa, (2) to study the methylation status of DNA repair genes between these groups, and (3) to assess the ancestry proportions of the study participants. Variations in methylation patterns will be detected between study groups. Methods: Archived formalin fixed paraffin-embedded (FFPE) prostate tumors (n=24) were collected through the Puerto Rico Biobank. Tumor specimens were classified as aggressive (n=11) and indolent (n=13) cases based on the Gleason scores (6+7(3+4) vs. 7(4+3)+8+9). Tumor areas and adjacent normal tissue were annotated on the H&E slides by a pathologist and extracted by macro-dissection. The Illumina 850K DNA methylation platform was used to measure DNA methylation patterns. The raw data was processed using minfi and normalized. Amount of missing values, histogram of β-values, principal component analysis (PCA) was to assess quality and to detect outliers. Results: A PCA model clearly separated the normal samples from the tumor samples. One of the most significantly differently methylated genes was AOX1. Further comparisons using TCGA PRAD data base revealed the predictable negative correlation between the gene expression and the average β-values. Regarding the PCa aggressiveness, 23 probes were identified as potential candidates using a p<0.001 and a Δβ-value of 0.2 as cut-off. These probes where located in six hypermethylated genes; RREB1, FAM71F2, JMJD1C, COL5A3, RAE1, GABRQ, and eleven hypomethylated; COL9A2, FAM179A, SLC17A2, PDE10A, PLEKHS1, TNNI2, OR51A4, RNF169, SPNS2, ADAMTSL5, and CYP4F12. Of the 179 candidate DNA repair genes. We found two significant differentially methylated DNA repair genes: JMJD1C and RNF169 between groups. The results from the ancestry proportions for African, European, and Indigenous American were: 24.1%, 64.2%, and 9% respectively. Conclusion: The identification of DNA methylation patterns related to PCa in Puerto Rican (PR) H/L men along with specific patterns related to aggressiveness and DNA repair constitutes a pivotal effort on the understanding of PCa disparities in this population. This constitutes a unique effort to provide an overview regarding methylation and ancestry patterns in PR H/L men. Acknowledgements; supported by U54 CA163071 and U54 CA163068-07 Citation Format: Jong Y. Park, Gilberto Ruiz-Deya, Jarline Encarnacion, Juile Dutil, Liang Wang, Carmen Ortiz Sanchez, Ryan Putney, Anders Berglund, Youngchul Kim, Jaime Matta. DNA methylation patterns between aggressive and indolent prostate tumors from Puerto Rican men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 781.