The Broad Institute's David Sabatini and colleagues report in Nature on their development and use of a method to uncover novel cancer targets. Their method uses a negative-selection RNAi screen that they then applied to find metabolic genes that are necessary for tumorigenesis in breast cancer. One gene they identified this way, phosphoglycerate dehydrogenase or PHGDH, is a catalyst in the serine biosynthesis pathway, and its protein levels are elevated in about 70 percent of ER-negative breast cancers. "These results reveal that certain breast cancers are dependent upon increased serine pathway flux caused by PHGDH over-expression and demonstrate the utility of in vivo negative-selection RNAi screens for finding potential anticancer target," Sabatini et al. write.
In Nature Genetics, Kenneth Kinzler at Johns Hopkins University School of Medicine and his team sequenced the exomes of 10 hepatitis C virus-associated hepatocellular carcinomas and found a novel mutation of ARID2. That mutation, they report, was found in four subtypes of hepatocellular carcinomas and that about 18 percent of people with hepatitis C virus-associated hepatocellular carcinoma had mutations that inactivated ARID2. This suggests "that ARID2 is a tumor suppressor gene that is relatively commonly mutated in this tumor subtype," the authors write.
Over in Nature Biotechnology, BGI-Shenzhen's Jun Wang and colleagues report the draft genome sequence of the Chinese hamster ovary-K1 ancestral cell line. Wang et al. say the assembly includes 2.45 gigabases of sequence and 24,383 predicted genes, and that it should be a useful tool for the community. "It is important to note that CHO-K1 is an ancestral cell line from which many CHO cell lines have been derived. During the course of the rather stringent manipulations involved in optimizing cell lines ... many genomic changes (e.g., SNPs, indels and other structural variations) have likely occurred owing to the inherent genomic instability of these cell lines," the authors add.