Epigenetic Germline Variants Predict Cancer Prognosis and Risk and Distribute Uniquely in Topologically Associating Domains.

Cancer is a highly heterogeneous disease caused by genetic and epigenetic alterations in normal cells. A recent study uncovered methylation quantitative trait loci (meQTLs) associated with different levels of local DNA methylation in cancers. Here, we investigated whether the distribution of cancer meQTLs reflected functional organization of the genome in the form of chromatin topologically associated domains (TADs), and evaluated whether cancer meQTLs near known driver genes have the potential to influence cancer risk or progression. At TAD boundaries, we observed differences in the distribution of meQTLs when one or both of the adjacent TADs was transcriptionally active, with higher densities near inactive TADs. Furthermore, we found differences in cancer meQTL distributions in active versus inactive TADs and observed an enrichment of meQTLs in active TADs near tumor suppressors, whereas there was a depletion of such meQTLs near oncogenes. Several meQTLs were associated with cancer risk in the UKBioBank, and we were able to reproduce breast cancer risk associations in the DRIVE cohort. Survival analysis in TCGA implicated a number of meQTLs in 13 tumor types. In 10 of these, polygenic meQTL scores were associated with increased hazard in a CoxPH analysis. Risk and survival-associated meQTLs tended to affect cancer genes involved in DNA damage repair and cellular adhesion and reproduced cancer-specific associations reported in prior literature. In summary, this study provides evidence that genetic variants that influence local DNA methylation are affected by chromatin structure and can impact tumor evolution.

Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response.

With the continued promise of immunotherapy for treating cancer, understanding how host genetics contributes to the tumor immune microenvironment (TIME) is essential to tailoring cancer screening and treatment strategies. Here, we study 1084 eQTLs affecting the TIME found through analysis of The Cancer Genome Atlas and literature curation. These TIME eQTLs are enriched in areas of active transcription, and associate with gene expression in specific immune cell subsets, such as macrophages and dendritic cells. Polygenic score models built with TIME eQTLs reproducibly stratify cancer risk, survival and immune checkpoint blockade (ICB) response across independent cohorts. To assess whether an eQTL-informed approach could reveal potential cancer immunotherapy targets, we inhibit CTSS, a gene implicated by cancer risk and ICB response-associated polygenic models; CTSS inhibition results in slowed tumor growth and extended survival in vivo. These results validate the potential of integrating germline variation and TIME characteristics for uncovering potential targets for immunotherapy.

Effects of Cold Plasma on Staphylococcus Aureus.

Objective: To investigate the effect of cold plasma on Staphylococcus aureus destruction at different treatment times. Materials and methods: Staphylococcus aureus was cultured on 4 plates of LB Agar medium each at 1.5 × 103 CFU / mL (colony-forming unit per milliliter) and one group was selected as the control group and the other 3 groups were treated with plasma for 5, 7 and 10 minutes. They were incubated for 24 hours at 37 °C. Finally, the number of colonies formed was counted. Results: It was shown that treatment with cold atmospheric plasma significantly reduced bacterial colonies and in comparison to the control plate with a colony count of 1.5 × 103 CFU/mL treatment with air plasma for 10 minutes decreased the Pseudomonas colony count to zero. Conclusion: It was observed that the cold atmospheric plasma jet device manufactured in atomic Energy Organization of Iran can significantly kill bacteria in a short time. Increasing the duration of treatment significantly reduces bacterial colonies.