Researchers from Harvard University, Stanford University, and Massachusetts General Hospital present a mathematical model to quantitatively explore the relationship between clonal diversity in metastatic tumors and seeding influx patterns from corresponding primary tumors. When the team applied this multitype continuous-time branching process-based framework to published datasets for dozens of ovarian, breast, or colorectal cancer samples from 15 individuals, it found evidence supporting a so-called "consecutive seeding model, in which cells from a given primary tumor contribute to metastases over multiple migration events. "From these clonally diverse metastases, under typical metastasis growth conditions, we find that 10 to 150 cells seeded each metastasis and left surviving lineages between initial formation and clinical detection," the authors report.
A University of Pennsylvania- and Children's Hospital of Philadelphia-led team takes a look at the relationship between mitochondrial DNA mutations and nuclear epigenome regulation. Using a combination of metabolic tracing, histone mass spectrometry, imaging, and other approaches, the researchers tallied nuclear histone modifications and levels of metabolite intermediates formed during the tricarboxylic acid cycle in cell lines with the same nuclear DNA sequences, but variable proportions of the same mitochondrial DNA mutation — an alteration previously implicated in diabetes, neuromuscular disease, and other metabolic or degenerative conditions. In the process, they saw "multiple associations between metabolites and histone modifications as the level of [mtDNA mutation] heteroplasmy increased," suggesting that mtDNA genotype "regulates the epigenome through mitochondrial metabolism."
Investigators in the US and India explore the roots of fluoroquinolone antibiotic resistance in Escherichia coli, focusing on a multidrug-resistant clonal group known as ST1193, which has been implicated in pandemic uropathogenic infections. The team brought together sequence data for more than 61,000 E. coli isolates from the Enterobase database, uncovering nearly 14,800 E. coli isolates containing quinolone resistance-determining region (QRDR) mutations involving two characteristic mutations in the DNA gyrase enzyme gene gyrA and one mutation in the topoisomerase IV gene parC. Based on their phylogenetic and comparative genomic analyses, the authors suggest that the fluoroquinolone resistance culprit mutations "are tightly associated genetically in naturally occurring strains," but arose through "11 simultaneous homologous recombination events involving [two] phylogenetically distant strains of E. coli" in the uropathogenic, drug resistant ST1193 clonal group.