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PLOS Studies on Tumor Suppressor Gene Modeling, Lung Cancer ctDNA, Bat Microbiomes

Using yeast modeling, a team from Memorial Sloan-Kettering Cancer Center and elsewhere took a closer look at cancer-related mutations identified through the center's MSKCC IMPACT clinical sequencing program, particularly those affecting genes involved in a Mre11 complex contributing to DNA damage response. As they report in PLOS Genetics, the researchers introduced 25 conserved MRE11 and RAD50 mutations in the yeast model organism Saccharomyces cerevisiae, identifying 10 mutated alleles that significantly dialed down the complex's ability to activate a downstream ATM kinase. From these and other results, the authors suggest that "signaling functions of the Mre11 complex are important for tumor suppression to a greater degree than its role in DNA repair."

For a paper in PLOS One, Korean researchers explore tumor features coinciding with the presence or absence of circulating tumor DNA (ctDNA) in the blood in three dozen individuals with non-small cell lung cancer. Using a PCR-based multiplex assay, the team searched for EGFR and KRAS gene mutations in matched ctDNA and formalin-fixed, paraffin-embedded tumor tissue samples, uncovering variable levels of ctDNA in the blood depending on patient's pathological tumor site, NSCLC subtype, and other clinicopathological features. "We suggest that primary or total tumor burden, solid adenocarcinoma morphology, tumor necrosis, and frequent mitosis could predict ctDNA shedding in pulmonary adenocarcinoma," the authors report. 

The gut microbiomes of insectivorous Mops condylurus bats become more similar to one another over time in bats living together in captivity, according to a team from Germany, Australia, and Cote d'Ivoire. The researchers did 16S ribosomal gene sequencing on fecal samples collected from 20 recently captured bats in Cote d'Ivoire, following up with a similar analysis done six weeks later. Because the gut microbiomes appear to converge in the bats, the authors argue that this "acclimatization period" may minimize variation between bats used in virus-reservoir studies and other infection-related research. "[T]hese findings imply that with the use of a short co-housing period of six weeks the fecal microbiome will become similar between disparate bats co-house in captivity," they conclude, noting that this approach "could be implemented to reduce the confounding effects of inter-animal variation in microbial communities for a more controlled experimental system."