Neighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors.

Importance: The biological processes that underlie the association of neighborhood environment with chronic diseases, such as cancer, remain poorly understood. Objective: To determine whether differences in breast tissue DNA methylation are associated with neighborhood deprivation among Black and White women with breast cancer. Design, Setting, and Participants: This cross-sectional study collected breast tissue from women undergoing surgery for breast cancer between January 1, 1993, and December 31, 2003. Participants were recruited through the University of Maryland Medical Center, with additional collection sites at Baltimore-area hospitals. Data analysis was performed from March 1 through December 1, 2022. Exposure: Year 2000 census tract-level socioeconomic deprivation measured via neighborhood deprivation index (NDI) as a standardized score, with Black and White race being ascertained through self-report. Main Outcome and Measures: The primary outcome was tissue DNA methylation using genome-wide measurements. The secondary outcome was tissue gene expression. Results: Participants included 185 women with breast cancer (110 Black [59.5%], 75 White [40.5%]). Mean (SD) age at surgery was 56.0 (14.1) years. Neighborhood deprivation was higher for Black women than for White women (Mean [SD] NDI, 2.96 [3.03] for Black women and -0.54 [1.91] for White women; difference, -3.50; 95% CI, -4.22 to -2.79; P < .001). In unstratified analysis, 8 hypomethylated CpG sites were identified as associated with the NDI, including sites in 2 tumor suppressor genes, LRIG1 and WWOX. Moreover, expression of the 2 genes inversely correlated with neighborhood deprivation. In the race-stratified analysis, the negative correlation between the LRIG1 gene body CpG site cg26131019 and the NDI remained significant in Black women. A neighborhood deprivation-associated decrease in gene expression was also observed for LRIG1 and WWOX in tumors from Black women. Conclusions and Relevance: In this study, high neighborhood deprivation was associated with differences in tissue DNA methylation and gene expression among Black women. These findings suggest that continued investment in public health interventions and policy changes at the neighborhood level may help to remedy biological alterations that could make minoritized populations more susceptible to chronic diseases.

DNA release from plant tissue using focused ultrasound extraction (FUSE).

Premise: Sample preparation in genomics is a critical step that is often overlooked in molecular workflows and impacts the success of downstream genetic applications. This study explores the use of a recently developed focused ultrasound extraction (FUSE) technique to enable the rapid release of DNA from plant tissues for genetic analysis. Methods: FUSE generates a dense acoustic cavitation bubble cloud that pulverizes targeted tissue into acellular debris. This technique was applied to leaf samples of American chestnut (Castanea dentata), tulip poplar (Liriodendron tulipifera), red maple (Acer rubrum), and chestnut oak (Quercus montana). Results: We observed that FUSE can extract high quantities of DNA in 9-15 min, compared to the 30 min required for control DNA extraction methods. FUSE extracted DNA quantities of 24.33 ± 6.51 ng/mg and 35.32 ± 9.21 ng/mg from American chestnut and red maple, respectively, while control methods yielded 6.22 ± 0.87 ng/mg and 11.51 ± 1.95 ng/mg, respectively. The quality of the DNA released by FUSE allowed for successful amplification and next-generation sequencing. Discussion: These results indicate that FUSE can improve DNA extraction efficiency for leaf tissues. Continued development of this technology aims to adapt to field-deployable systems to increase the cataloging of genetic biodiversity, particularly in low-resource biodiversity hotspots.

Immunological Effects of Histotripsy for Cancer Therapy.

Cancer is the second leading cause of death worldwide despite major advancements in diagnosis and therapy over the past century. One of the most debilitating aspects of cancer is the burden brought on by metastatic disease. Therefore, an ideal treatment protocol would address not only debulking larger primary tumors but also circulating tumor cells and distant metastases. To address this need, the use of immune modulating therapies has become a pillar in the oncology armamentarium. A therapeutic option that has recently emerged is the use of focal ablation therapies that can destroy a tumor through various physical or mechanical mechanisms and release a cellular lysate with the potential to stimulate an immune response. Histotripsy is a non-invasive, non-ionizing, non-thermal, ultrasound guided ablation technology that has shown promise over the past decade as a debulking therapy. As histotripsy therapies have developed, the full picture of the accompanying immune response has revealed a wide range of immunogenic mechanisms that include DAMP and anti-tumor mediator release, changes in local cellular immune populations, development of a systemic immune response, and therapeutic synergism with the inclusion of checkpoint inhibitor therapies. These studies also suggest that there is an immune effect from histotripsy therapies across multiple murine tumor types that may be reproducible. Overall, the effects of histotripsy on tumors show a positive effect on immunomodulation.