Researchers at Columbia University Medical Center's Institute for Cancer Genetics and their colleagues this week report in a Science paper published online in advance on their investigation of 97 glioblastoma multiforme tumor samples. They found that three samples harbored "oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor genes (FGFR1 or FGFR3) to the transforming acidic coiled-coil coding domains of TACC1 or TACC3, respectively."
In this week's issue, Dana-Farber Cancer Institute's William Kaelin discusses the challenges scientists have encountered in RNAi research. "As with any new technology, the initial euphoria is now being tempered by a growing awareness of the pitfalls," Kaelin writes in Science. A prominent problem, he says, is the potential for off-target effects when using siRNA or shRNA. "These issues are potentially compounded by problems related to multiple hypothesis testing when large si/shRNA libraries are used in high-throughput screens," he adds. Because of this, Kaelin says that "in the short term, one approach would be to conduct more focused screens, perhaps involving fewer than 100 genes, to allow deeper interrogation of primary screen hits in lower-throughput secondary screens." Later on, as technologies and techniques advance, "the performance of genome-scale screens will improve with further library enhancements (including increasing the number of si/shRNAs per gene and eliminating si/shRNA empirically found to produce false-positives across multiple screens), the use of algorithms that take into account si/shRNA knockdown efficiencies, and incorporation of orthogonal data sets (for example, data from genomic studies or chemical screens)," he adds.
Over in Science Signaling, investigators from Duke University Medical Center show in a mouse model that "p53 [functions] in endothelial cells to protect mice from myocardial injury after whole-heart irradiation." Further, the Duke-led team adds that "mice with an endothelial cell-specific deletion of p53 succumbed to heart failure after whole-heart irradiation as a result of myocardial necrosis, systolic dysfunction, and cardiac hypertrophy."