WASHINGTON UNIVERSITY IN ST. LOUIS

By mapping intracellular mutations onto an atomic model of Kir1.1, we found that several are localized to an immunoglobulin (Ig)-like domain (IgLD). Thermodynamic calculations on computationally mutated channels suggest that the IgLD core residues are among the most important residues for determining cytoplasmic domain stability. Consistent with this notion, we show that two Antenatal Barter Syndrome mutations located within the IgLD core impair channel biosynthesis and trafficking in mammalian cells. Our study sheds new light on the pathogenesis of ABD and establishes the IgLD as an essential structure within the Kir channel family... In analyzing the tumor from a patient, we identified a novel EGFR alteration in lung cancer: EGFR exon 18-25 kinase domain duplication (EGFR-KDD). Through analysis of a larger cohort of tumor samples, we found additional cases of EGFR-KDD in lung, brain, and other cancers. Given the presence of two tandem in-frame kinase domains within the EGFR-KDD..

Primary location: St. Louis United States