Epigenome-wide association study of prostate cancer in African American men identified differentially methylated genes.

Introduction: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide.

Methods: This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs.

Clonal Hematopoiesis in Patients With Human Immunodeficiency Virus and Cancer.

Background: Cancer-related deaths for people with human immunodeficiency virus (PWH) are increasing due to longer life expectancies and disparately poor cancer-related outcomes. We hypothesize that advanced biological aging contributes to cancer-related morbidity and mortality for PWH and cancer. We sought to determine the impact of clonal hematopoiesis (CH) on cancer disparities in PWH.

Identification of a Biomarker Panel from Genome-Wide Methylation to Detect Early HPV-Associated Oropharyngeal Cancer.

Unlabelled: As oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) increases in men, the need for a screening test to diagnose OPC early is crucial. This study agnostically identified differentially methylated CpG sites to identify additional biomarkers to improve screening for early OPC.DNA was extracted from oral gargles of 89 early cases and 108 frequency matched healthy controls, and processed for genome-wide methylation using the Illumina Infinium MethylationEPIC BeadChip.

Differences in epigenetic age by HIV status among patients with a non-AIDS defining cancer.

Objective: People with HIV (PWH) are living longer and experiencing higher numbers of non-AIDS-defining cancers (NADC). Epigenetic aging biomarkers have been linked to cancer risk, and cancer is now a leading cause of death in PWH, but these biomarkers have not been investigated in PWH and cancer.

Design: In order to compare epigenetic age by HIV status, HIV-uninfected participants were matched to PWH by reported age, tumor site, tumor sequence number, and cancer treatment status.

Elevated Methionine Flux Drives Pyroptosis Evasion in Persister Cancer Cells.

Unlabelled: Induction of cell death represents a primary goal of most anticancer treatments. Despite the efficacy of such approaches, a small population of "persisters" develop evasion strategies to therapy-induced cell death. While previous studies have identified mechanisms of resistance to apoptosis, the mechanisms by which persisters dampen other forms of cell death, such as pyroptosis, remain to be elucidated.

Proteogenomic, Epigenetic, and Clinical Implications of Recurrent Aberrant Splice Variants in Clear Cell Renal Cell Carcinoma.

Background: Alternative mRNA splicing can be dysregulated in cancer, resulting in the generation of aberrant splice variants (SVs). Given the paucity of actionable genomic mutations in clear cell renal cell carcinoma (ccRCC), aberrant SVs may be an avenue to novel mechanisms of pathogenesis.

Objective: To identify and characterize aberrant SVs enriched in ccRCC.

Epigenetic dysregulation of immune-related pathways in cancer: bioinformatics tools and visualization.

Cancer immune evasion is one of the hallmarks of carcinogenesis. Cancer cells employ multiple mechanisms to avoid immune recognition and suppress antitumor immune responses. Recently, accumulating evidence has indicated that immune-related pathways are epigenetically dysregulated in cancer.

Accessible Pipeline for Translational Research Using TCGA: Examples of Relating Gene Mechanism to Disease-Specific Outcomes.

Bioinformatic scientists are often asked to do widespread analyses of publicly available datasets in order to identify genetic alterations in cancer for genes of interest; therefore, we sought to create a set of tools to conduct common statistical analyses of The Cancer Genome Atlas (TCGA) data. These tools have been developed in response to requests from our collaborators to ask questions, validate findings, and better understand the function of their gene of interest. We describe here what data we have used, how to obtain it, and what figures we have found useful.

Methylation of immune synapse genes modulates tumor immunogenicity.

Cancer immune evasion is achieved through multiple layers of immune tolerance mechanisms including immune editing, recruitment of tolerogenic immune cells, and secretion of immunosuppressive cytokines. Recent success with immune checkpoint inhibitors in cancer immunotherapy suggests a dysfunctional immune synapse as a pivotal tolerogenic mechanism. Tumor cells express immune synapse proteins to suppress the immune system, which is often modulated by epigenetic mechanisms.

Suppression of STING signaling through epigenetic silencing and missense mutation impedes DNA damage mediated cytokine production.

The production of cytokines in response to DNA-damage events may be an important host defense response to help prevent the escape of pre-cancerous cells. The innate immune pathways involved in these events are known to be regulated by cellular molecules such as stimulator of interferon genes (STING), which controls type I interferon and pro-inflammatory cytokine production in response to the presence of microbial DNA or cytosolic DNA that has escaped from the nucleus. STING signaling has been shown to be defective in a variety of cancers, such as colon cancer and melanoma, actions that may enable damaged cells to escape the immunosurveillance system.

Expanding epigenomics to archived FFPE tissues: an evaluation of DNA repair methodologies.

Background: Epigenome-wide association studies are emerging in the field of cancer epidemiology with the rapid development of large-scale methylation array platforms. Until recently, these methods were only valid for DNA from flash frozen (FF) tissues. Novel techniques for repairing DNA from formalin-fixed paraffin-embedded (FFPE) tissues have emerged; however, a direct comparison of FFPE DNA repair methods before analysis on genome-wide methylation array to matched FF tissues has not been conducted.