In Science this week, two groups publish studies offering clues about the genetics behind cancer susceptibility to immune checkpoint inhibition. In the first, researchers used CRISPR screening on a mouse melanoma cell line resistant to immune checkpoint inhibitors to identify several genes whose inactivation enhanced tumor sensitivity to such drugs, including three — Pbrm1, Arid2, and Brd7 — that produce proteins part of a chromatin remodeling complex. In the second study, whole-exome sequencing was performed on patients with clear-cell rental cell carcinoma. Those whose tumors harbored inactivating mutations in one of the chromatin remodeling complex genes identified in the first study had better responses to immune checkpoint inhibitors. Further analysis in additional patients showed that loss-of-function mutations in Pbrm1 correlated with better response to immunotherapy. GenomeWeb has more on these studies, here.
Also in Science, a multi-institute research team reports a new low-cost and scalable method for gene synthesis. Called DropSynth, the approach uses a library of barcoded beads that pull down the oligonucleotides necessary for a gene's assembly, which are then processed and assembled in water-in-oil emulsions. The scientists used the method to build more than 7,000 synthetic genes that encode two essential proteins in Escherichia coli and say that DropSynth may be used to rapidly test thousands of synthetic gene designs in workflows that can be performed by individual scientists in pooled formats.