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PLOS Papers on E. Coli DSB Repair, Pancreatic Cancer ctDNA, Arteriovenous Malformation Mutations

In PLOS Genetics, researchers from the UK and the US explore the consequences of double-strand DNA break repair in Escherichia coli. The team relied on genome sequencing, flow cytometry, cell imaging, and other approaches to follow E. coli cells through the process of chromosomal replication and cell division after introducing double-strand breaks. "Our results demonstrate that this perturbation does not alter the average cell size at initiation of DNA replication or initiation of cell division," the authors write, noting that increased DNA double-strand break repair "does delay the segregation of the DNA to daughter cells and the completion of cell division, explaining the increase in average cell size observed previously."

A team from Japan tracks KRAS mutations in circulating tumor DNA samples collected from individuals with localized or metastatic pancreatic ductal adenocarcinoma (PDAC). As they report in PLOS One, the researchers characterized KRAS mutation in 422 blood samples from 78 pancreatic cancer patients, including 67 cases with corresponding tumor samples. By comparing tumor and ctDNA profiles, as well as the longitudinal ctDNA patterns in the patients receiving surgery or chemotherapy treatment, they saw ties between better outcomes and the absence of ctDNA KRAS mutation emergence after treatment. "Our study showed the significance of sequential KRAS ctDNA assessments for predicting prognosis and therapeutic responses in patients with PDAC via longitudinal monitoring," they write, noting that "one time assessment of KRAS-mutated ctDNA before surgery or chemotherapy was not clearly associated with recurrence and prognosis."

For another PLOS One study, investigators from Harvard Medical School, Boston Children's Hospital, and Massachusetts General Hospital take a look at somatic mutations in more than a dozen cases of intracranial arteriovenous malformation (AVM), a condition marked unusual vein and artery connections that can hemorrhage or cause other symptoms. Using multiplex, molecular inversion probe sequencing, the team searched for mutations in 16 sporadic, intracranial AVM brain samples, focusing on KRAS and a handful of other genes with suspected ties to the condition. The search uncovered mutations in the KRAS or BRAF10 samples — results the authors confirmed with ddPCR assays.