In a paper published online in advance in Nature this week, members of the Wellcome Trust Sanger Institute's Cancer Genome Project, along with their international colleagues, report that the SWI/SNF chromatin remodeling complex gene PBRM1 is frequently mutated in renal carcinomas. By sequencing the exomes in a series of primary clear cell carcinomas, the CGP-led team found truncating mutations in PBRM1 in 41 percent of cases. "These data further elucidate the somatic genetic architecture of ccRCC and emphasize the marked contribution of aberrant chromatin biology," the authors write.
A research team co-led by investigators at Canada's Campbell Family Institute for Cancer Research and the Ontario Cancer Institute reports in a Nature advance online publication the "evolution of human BCR-ABL1 lymphoblastic leukemia-initiating cells." Using xenografting techniques and copy-number alteration profiling methods, the team shows that "many diagnostic patient samples contain multiple genetically distinct leukemia-initiating cell subclones," which it says underscores researchers' "development of therapies that eradicate all intra-tumoral subclones."
Stirling Churchman and Jonathan Weissman at the University of California, San Francisco, debut their native elongating transcript sequencing — or NET-seq — approach. This method harnesses data generated by "deep sequencing of 3′ ends of nascent transcripts associated with RNA polymerase" and enables researchers "to monitor transcription at nucleotide resolution," they say. Using NET-seq, Churchman and Weissman found "pervasive polymerase pausing and backtracking throughout the body of transcripts" in S. cerevisiae. This "nucleosome-induced pausing represents a major barrier to transcriptional elongation in vivo," the authors write.
In another Nature advance online publication, researchers at the Israel Institute of Technology describe their generation of patient/disease-specific induced pluripotent stem cells for a person with type 2 congenital long QT syndrome. Using the resulting "LQTS human iPSC-derived cardiac-tissue model," the team was able to "evaluate the potency of existing and novel pharmacological agents."