Tumor genetic testing is standard of care for patients with advanced lung adenocarcinoma but the fraction of patients who derive clinical benefit remains undefined. Here, we report the experience of 860 patients with metastatic lung adenocarcinoma analyzed prospectively for mutations in >300 cancer-associated genes. Potentially actionable genetic events were stratified into one of four levels based upon published clinical or laboratory evidence that the mutation in question confers increased sensitivity to standard or investigational therapies. Overall 37.1% (319/860) of patients received a matched therapy guided by their tumor molecular profile. Excluding alterations associated with standard of care therapy, 14.4% (69/478) received matched therapy with a clinical benefit of 52%. Use of matched therapy was strongly influenced by the level of pre-existent clinical evidence that the mutation identified predicts for drug response. Analysis of genes mutated significantly more often in tumors without known actionable mutations nominated STK11 and KEAP1 as possible targetable mitogenic drivers.

Many mutations in cancer are of unknown functional significance. Standard methods use statistically significant recurrence of mutations in tumor samples as an indicator of functional impact. We extend such analyses into the long tail of rare mutations by considering recurrence of mutations in clusters of spatially close residues in protein structures. Analyzing 10,000 tumor exomes, we identify more than 3000 rarely mutated residues in proteins as potentially functional and experimentally validate several in RAC1 and MAP2K1. These potential driver mutations (web resources: 3dhotspots.org and cBioPortal.org) can extend the scope of genomically informed clinical trials and of personalized choice of therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0393-x) contains supplementary material, which is available to authorized users.

One of the challenges for achieving efficient exciton transport in solar energy conversion systems is precise structural control of the light-harvesting building blocks. Here, we create a tunable material consisting of a connected chromophore network on an ordered biological virus template. Using genetic engineering, we establish a link between the inter-chromophoric distances and emerging transport properties. The combination of spectroscopy measurements and dynamic modelling enables us to elucidate quantum coherent and classical incoherent energy transport at room temperature. Through genetic modifications, we obtain a significant enhancement of exciton diffusion length of about 68% in an intermediate quantum-classical regime.

<p>Breakdown of MAP2K1, RAF1, ARAF, FGFR3-TACC3 fusion and CDKN2A loss patients</p>

<p>Patient 1 Concurrent EGFR and KRAS mutations in a patient identified by MSK-IMPACT</p>