Researchers from the US, Japan, and Turkey describe germline changes in the Bloom syndrome-related gene that appear to boost mesothelioma risk in individuals exposed to asbestos. Starting with 10 familial mesothelioma patients from four affected families in Turkey, the team used genome sequencing to focus in on a truncating frameshift mutation that affected one copy of the BLM gene in a mother and son with mesothelioma from one of the families. With targeted BLM sequencing on 29 more patients from the US or Turkey, they found another BLM mutation in an American woman with mesothelioma and in two of her siblings, including a brother with a history of melanoma and mesothelioma. And pathogenic BLM mutations turned up in five of the 122 exome-sequenced individuals treated for sporadic mesothelioma at the National Cancer Institute, prompting a series of follow-up experiments to characterize the functional impacts of heterozygous BLM mutations in human cell lines and in mouse models.
A team from the University of Maryland, the University of Alabama, and Yale University presents a transcriptome atlas generated by profiling Streptococcus pneumoniae in vivo in several mouse tissue types. The researchers did RNA sequencing on blood, kidney, lung, heart, and nasopharynx tissue samples from control, S. pneumoniae-colonized, or S. pneumoniae-infected mice, producing transcriptomes to explore host interactions with three S. pneumoniae strains. "The in vivo bacterial transcriptome during colonization/disease was distinct from previously reported in vitro transcriptomes," they report, adding that "[w]e identified and experimentally verified host-defense pathways induced by [S. pneumoniae] during invasive disease, including proinflammatory responses and the interferon response."
Investigators at Wenzhou Medical University and elsewhere report on the roots of retinoblastoma, informed by single-cell sequencing on organoid models of the childhood retinal malignancy. Using gene-edited human embryonic stem cells, they came up with retinal organoid models that "exhibit properties highly consistent with [retinoblastoma] tumorigenesis, transcriptome, and genome-wide methylation." When the team tracked tumorigenesis in these retinal organoids, it saw signs that the tumor cells originated from maturing cone precursor cells that express the ARR3 marker, and were characterized by higher-than-usual levels of a spleen tyrosine kinase enzyme and the PI3 kinase-Akt pathway that it activated. In contrast, the authors note, "SYK inhibitors led to remarkable cell apoptosis in cancerous organoids."