In an advance, online publication of Nature this week, investigators at the University of Southern California and their colleagues report their use of homologous recombination to engineer genes and create p53-knockout rats. The team created a targeting vector to disrupt p53, enabling the "p53 gene-targeted mutation in the rat ES cell genome" to "transmit through the germ line via ES-cell rat chimeras," creating the knockout rats, which the authors call "a powerful new platform for the study of human disease."
Yale University's Frank Slack and colleagues this week show that "tumors can become addicted to oncomiRs." Specifically, the team highlights the potential therapeutic value of "oncogenic addiction." Slack et al. used "Cre and Tet-off technologies to generate mice conditionally expressing miR-21," and show that "overexpression of miR-21 leads to a pre-B malignant lymphoid-like phenotype, demonstrating that mir-21 is a genuine oncogene." Upon the inactivation of miR-21, tumors regressed within a few days, "partly as a result of apoptosis."
David Bartel at the Whitehead Institute and his colleagues suggest in Nature this week that "mammalian microRNAs predominantly act to decrease target mRNA levels." Using ribosome profiling, Bartel et al. found that "for both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most ... of the decreased protein production," demonstrating that "changes in mRNA levels closely reflect the impact of miRNAs on gene expression," the authors write.
Investigators at Genentech and their collaborators describe the diversity of somatic mutation patterns and pathway alterations in human cancers. The team reports its "identification of 2,576 somatic mutations across [about] 1,800 megabases of DNA representing 1,507 coding genes from 441 tumors comprising breast, lung, ovarian, and prostate cancer types and subtypes." The authors show that mutation rates vary "substantially across tumor types and subtypes," and suggest that their study "provides an overview of the mutational spectra across major human cancers and identifies several potential therapeutic targets."