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

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

Iridium/silicon multilayers for extreme ultraviolet applications in the 20-35 nm wavelength range

We have developed an Ir/Si multilayer for extreme ultraviolet (EUV) applications. Normal incidence reflectance measurements of a prototype film tuned to 30nm wavelength show superior performance relative to a conventional Mo/Si multilayer structure; we also find good stability over time. Transmission electron microscopy and electron dispersive x-ray spectroscopy have been used to examine the microstructure and interface properties of this system: we find amorphous Si layers and polycrystalline Ir layers, with asymmetric interlayer regions of mixed composition. Potential applications of Ir/Si multilayers include instrumentation for solar physics and laboratory EUV beam manipulation