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PLOS Papers on Breast Cancer Methylation, COVID 'Omics, Canine Hematopoietic Cancer Risk

A team from Roswell Park Comprehensive Cancer Center compares DNA methylation patterns in breast cancer samples from women of African or European ancestry with estrogen receptor-negative or -positive forms of the disease for a paper in PLOS One. Using array-based methylation profiling, the team assessed breast tumor samples from 58 African-American and 80 European-American women, focusing on hundreds of differentially methylated loci that distinguished ER-positive or ER-negative tumors or tumors from women from different ancestral backgrounds. After validating the differentially methylated sites in samples from the Cancer Genome Atlas set, the authors explored their potential ties to miRNA target genes and related pathways — from cell cycle and cytoskeletal remodeling pathways to those involved in angiogenesis and cell signaling. "These findings support the involvement of epigenetic regulation of miRNA expression and provide insights into the relations of clinical[ly]-relevant miRNAs to their target genes," they write, "which may serve as potential preventative and therapeutic targets."

For a paper in PLOS Pathogens, researchers in France report on findings from a multi-omic analysis of nasopharyngeal swab samples collected from individuals diagnosed with COVID-19 during the first wave of the pandemic. Starting with more than 1,200 SARS-CoV-2-positive samples, the team did shotgun metagenomic sequencing, phylogenetics, and other analyses on samples from 104 patients with sufficient RNA for transcriptomic analyses, including 45 patients who required intensive care, 17 hospitalized COVID-19 patients, and 42 treated in an outpatient setting. Together, the authors say, their results suggest that "the most severe cases of COVID-19 are characterized by the presence of over-active immune cells resulting in neutrophil pulmonary infiltration which, in turn, could enhance the inflammatory response and prolong tissue damage."

In PLOS Genetics, a French National Center for Scientific Research-led team explores variants involved in the risk of histiocytic sarcoma and other hematopoietic cancers in dogs from Bernese mountain dog, Rottweiler, flat-coated retriever, and golden retriever breeds. Based on their approach — which included genome-wide association studies on histiocytic sarcoma, lymphoma, and mast cell tumors, along with targeted sequencing — the researchers saw potentially additive risk haplotypes in dogs that coincided with parts of the human genome that have been implicated in cancer risk and immune-related phenotypes. "Capture and targeted sequencing of specific loci suggested the existence of regulatory variants in non-coding regions and methylation mechanisms linked to risk haplotypes, which lead to strong cancer predisposition in specific dog breeds," they report, noting that seemingly additive nature of the loci "illustrates the pleiotropic nature of these canine cancer loci as observed in human oncology."