Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

Background: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. Methodology: We developed and implemented an optimized mutation profiling platform (“OncoMap”) to interrogate ∼400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. Conclusions: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of “actionable” cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents

Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples

BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap") to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Il Disegno dell'architettura antica. Nuovi codici per la comprensione e la fruizione. Tecniche di SFM per il rilievo de "La Pianta di Mausoleo con Giardino", collocata al Lapidarium del Palazzo Ducale di Urbino

La ricerca riguarda i disegni di architettura del mondo greco romano, poco numerosi e ancora inesplorati nelle loro particolari caratteristiche. Uno dei disegni più preziosi di questo patrimonio è una incisione su lastra marmorea che si trova nel lapidario del Palazzo Ducale di Urbino. Grazie ad acquisizioni fotografiche con tecniche macro e a metodiche SFM è stato possibile ottenere un modello 3D per l’estrazione di elaborati bidimensionali per nuove possibilità di studio, di catalogazione e di fruizione digitale del disegno

Sensorial, biochemical and molecular changes in Raboso Piave grape berries applying "Double Maturation Raisonnee" and late harvest techniques

The aim of this work was to investigate sensorial, biochemical, and molecular changes in Raboso Piave grape berries subjected to delayed harvests as Late Harvest (LH) and "Double Maturation Raisonnee" (DMR) techniques. At the molecular level, a microarray study was conducted comparing Traditional Harvest berries (TH) to LH and DMR ones. Gene ontology enrichment analysis pointed out that LH and DMR techniques affected metabolism of acids, sugars and polyphenols. A Principal Component Analysis, performed on transcriptomic data, pointed out that malate catabolism as well as some branches of flavonoids biosynthesis are significantly affected by DMR. In DMR grape berries, the flavonol and catechin accumulations were induced and depressed, respectively. In parallel, the transcription of flavonol synthase and leucoanthocyanidin-reductase 2, the main genes responsible for flavonol and catechin biosynthesis, were similarly induced and down-regulated. These changes resulted in a brighter colored wine with lower astringency. (C) 2013 Elsevier Ireland Ltd. All rights reserved

Thermal analysis experiment to evaluate the stability of multilayer coatings in a space environment close to the sun

The next SOLO (SOLar Orbiter) mission will carry onboard the METIS (Multi Element Telescope for Imaging and Spectroscopy) instrument which will perform broad-band and polarized imaging of the visible K-corona and narrow-band imaging of the UV (HI Ly \u3b1, 121.6 nm) and EUV (He II Ly \u3b1, 30.4 nm) corona as well as in the visible spectral range. Several multilayer optics with high reflectivity in the all ranges of interest have been studied. Since SOLO will fly at the short distance from the Sun of 0.23 AU at its perihelion, a careful determination of the heat load and the solar wind effect on the multilayers must be carried in order to check if degradation occurs. To test thermal stability, a thermal analysis experiment has been conceived: the proposed multilayer structures, which are based on different pairs of materials and different capping layers design, must be subjected both to heating and cooling, reproducing the temperatures experienced in orbit. Reflectance in the EUV range of interest has been measured before and after each treatment to verify possible degradation

Multilayer mirrors for FERMI@ELETTRA beam transport system

Experiments performed in a Free Electron Laser (FEL) facility can require a selection of higher harmonics; a typical example is the pump and probe experiments in which the system under test is pumped with a fundamental wavelength and probed with its third harmonic. The wavelengths selection performed by a monochromator can affect beam properties such as wavefront deformation or time elongation and its usage in the beam manipulation should be avoided. Nevertheless, for a limited number of wavelengths, the selection can be performed using periodic multilayer coatings (MLs) with the reflectivity peak tuned at the desired harmonic: this technique is already foreseen at the new FERMI@Elettra FEL facility for selecting 20nm, 16nm, 13.5nm and 6.66nm harmonics. In order to improve the fundamental rejection, the MLs have been overcoated by different capping-layers; in particular at shortest wavelength higher rejection ratio have been obtained by the use of a third absorbent material in the capping layer. However, this same approach has not showed considerable improvements at the longest wavelengths, where interferential aperiodic capping-layers designed using a method based on the control of standing wave distribution are to be preferred

Multilayer optics to be used as FEL fundamental suppressors for harmonics selection

Pump and probe experiments are one of themost attractive and powerful tools offered by a free electron laser facility. In these experiments it is fundamental to pump the system with a particular wavelength (usually the fundamental one) and to probe it with a second wavelength (e.g. higher emitted harmonics). Radiation emitted at the fundamental wavelength is 100 or more times the number of photons emitted in higher harmonics; selection of higher harmonics can be therefore critical.Multilayer (ML) mirrors that are able to provide high reflectivity peak at the desired harmonic wavelength while rejecting the fundamental have been designed and their application is foreseen to the FERMI@Elettra FEL beam transport system. The photon beam will be split into two and one of these will pass through a set ofML mirrors optimized for third harmonics selection; this scheme is also useable to realize a delay line inwhich the few nanosecond time delay will be controlled by changing the mirrors distance. A set of target wavelengths has been considered and multilayer structure materials have been selected. The MLs have been designed using a method based on the control of standing wave distribution at the fundamental and third harmonics wavelength, using a capping layer as a key element to achieve the willing rejection. Fabrication and test of such structures are foreseen