In PLOS Genetics, researchers from Korea and Germany delved into the roots of genome instability in forms of an autoimmune disease called Aicardi-Goutières syndrome (AGS) that involves SAMHD1 mutations. Using a DNA-RNA hybrid immunoprecipitation sequencing (DRIP-seq) strategy, the team profiled so-called "R-loops" formed at parts of the genome with transcription-replication conflicts in fibroblast samples from individuals with AGS, focusing on fibroblasts from patients who had AGS-related mutations in SAMHD1 or other AGS-associated genes. The R-loops were enhanced in fibroblasts with lower-than-usual SAMHD1 levels, the authors note, suggesting that wild type version of SAMHD1 may act to remove R-loops, while mutations that dial down its expression lead to genomic instability and boost cancer risk. "Our findings provide insight into the molecular and mechanical understanding of the autoimmunity and cancer co-morbidity [for AGS]," they write, "and suggest that SAMHD1 and R-loops are potential and reliable biomarkers in anti-cancer therapeutics."
A team from Colombia and the US takes a look at SARS-CoV-2 introductions to the Colombian Amazon for a paper in PLOS Neglected Tropical Diseases. After generating whole-genome sequences for SARS-CoV-2 isolates from 52 Indigenous and seven non-Indigenous individuals tested at home or in a hospital setting in the Amazonian basin region, the researchers brought in data for more than 9,700 more SARS-CoV-2 genomes sequenced in Colombia, Brazil, and other parts of the world, identifying 10 viral lineages and at least two SARS-CoV-2 introductions to the region from local sources and from other parts of South America. "Our results showed two independent introductions of the virus into the [Colombian Amazonas] department," the authors explain, noting that "one of these associated with asymptomatic cases."
For a paper in PLOS One, investigators in Korea compare microRNA profiles of nearly 200 tumor samples spanning 14 cancer types, narrowing in on a handful of miRNAs that distinguish liver cholangiocarcinomas from metastases to the liver by adenocarcinomas originating in other parts of the body. With array-based miRNA testing on 195 primary tumor samples from liver, colorectal cancer, breast, ovarian, and other cancer types, the team uncovered enhanced expression of the miRNA miR-30a and muted expression of miRNAs such as miR-200c, miR-141, and miR-425 in primary intrahepatic cholangiocarcinoma samples — profiles that distinguished the liver cancer from adenocarcinoma metastases to the liver with nearly 85 percent accuracy. "Although the present data requires further validation using broader and larger datasets, our results provide important clues for differentiating between adenocarcinoma tissue origins in the liver, especially for the diagnosis of gastrointestinal cancer metastases," the authors conclude.