In this week's Science Translational Medicine, an international team of researchers reports on the discovery of genetic mutations in a muscle protein gene that can lead to a heart condition called dilated cardiomyopathy. The disease is commonly caused by mutations in the gene TNN, which encodes a large protein called titin that is involved in muscle structure, flexibility, and stability. However, genetic variations of TNN are common, and many people who carry mutations never develop disease. In an effort to identify harmful mutations from benign ones, the researchers sequenced TNN from more than 5,200 individuals, both healthy and with dilated cardiomyopathy, and found that the mutations most likely to cause the disorder are located towards one particular end of titin. Mutations in healthy individuals typically occur at other parts of the protein, allowing it to function normally. GenomeWeb has more on this study here.
In Science Translational Medicine, an international group of researchers describes the development of a new test to identify which tumors will best respond to cancer drugs targeting epidermal growth factor receptor (EGFR). Aberrant activation of EGFR signaling plays a role in the initiation, progression, and resistance of certain tumors, but existing genetic analysis approaches often fail to identify such dysregulation. To address this, the team developed a test that detects the interaction between EGFR and the signaling molecule GRB2. In human tumor samples and in xenograft mice, the test was able to identify cancers with higher levels of EGFR-GRB2 complexes, which indicate that the tumors are more likely to respond to anti-EGFR therapy.