BackgroundNon-small cell lung cancer (NSCLC) is a heterogeneous group of disorders with a number of genetic and proteomic alterations. c-CBL is an E3 ubiquitin ligase and adaptor molecule important in normal homeostasis and cancer. We determined the genetic variations of c-CBL, relationship to receptor tyrosine kinases (EGFR and MET), and functionality in NSCLC.Methods and FindingsUsing archival formalin-fixed paraffin embedded (FFPE) extracted genomic DNA, we show that c-CBL mutations occur in somatic fashion for lung cancers. c-CBL mutations were not mutually exclusive of MET or EGFR mutations; however they were independent of p53 and KRAS mutations. In normal/tumor pairwise analysis, there was significant loss of heterozygosity (LOH) for the c-CBL locus (22%, n = 8/37) and none of these samples revealed any mutation in the remaining copy of c-CBL. The c-CBL LOH also positively correlated with EGFR and MET mutations observed in the same samples. Using select c-CBL somatic mutations such as S80N/H94Y, Q249E and W802* (obtained from Caucasian, Taiwanese and African-American samples, respectively) transfected in NSCLC cell lines, there was increased cell viability and cell motility.ConclusionsTaking the overall mutation rate of c-CBL to be a combination as somatic missense mutation and LOH, it is clear that c-CBL is highly mutated in lung cancers and may play an essential role in lung tumorigenesis and metastasis.
We demonstrate electrical spin injection from ferromagnetic Fe/Tb multilayer structures with remanent perpendicular magnetization into GaAs-based light-emitting diodes at room temperature. Using a reverse-biased Schottky contact and a MgO tunnel contact, respectively, we achieve spin injection at remanence. The maximum degree of circular polarization of the emitted light is 3% at room temperature.
BackgroundCancer-related genes show racial differences. Therefore, identification and characterization of DNA copy number alteration regions in different racial groups helps to dissect the mechanism of tumorigenesis.MethodsArray-comparative genomic hybridization (array-CGH) was analyzed for DNA copy number profile in 40 Asian and 20 Caucasian lung cancer patients. Three methods including MetaCore analysis for disease and pathway correlations, concordance analysis between array-CGH database and the expression array database, and literature search for copy number variation genes were performed to select novel lung cancer candidate genes. Four candidate oncogenes were validated for DNA copy number and mRNA and protein expression by quantitative polymerase chain reaction (qPCR), chromogenic in situ hybridization (CISH), reverse transcriptase-qPCR (RT-qPCR), and immunohistochemistry (IHC) in more patients.ResultsWe identified 20 chromosomal imbalance regions harboring 459 genes for Caucasian and 17 regions containing 476 genes for Asian lung cancer patients. Seven common chromosomal imbalance regions harboring 117 genes, included gain on 3p13-14, 6p22.1, 9q21.13, 13q14.1, and 17p13.3; and loss on 3p22.2-22.3 and 13q13.3 were found both in Asian and Caucasian patients. Gene validation for four genes including ARHGAP19 (10q24.1) functioning in Rho activity control, FRAT2 (10q24.1) involved in Wnt signaling, PAFAH1B1 (17p13.3) functioning in motility control, and ZNF322A (6p22.1) involved in MAPK signaling was performed using qPCR and RT-qPCR. Mean gene dosage and mRNA expression level of the four candidate genes in tumor tissues were significantly higher than the corresponding normal tissues (P<0.001~P=0.06). In addition, CISH analysis of patients indicated that copy number amplification indeed occurred for ARHGAP19 and ZNF322A genes in lung cancer patients. IHC analysis of paraffin blocks from Asian Caucasian patients demonstrated that the frequency of PAFAH1B1 protein overexpression was 68% in Asian and 70% in Caucasian.ConclusionsOur study provides an invaluable database revealing common and differential imbalance regions at specific chromosomes among Asian and Caucasian lung cancer patients. Four validation methods confirmed our database, which would help in further studies on the mechanism of lung tumorigenesis.
We demonstrate a photodetector with ferromagnetic contacts which can electrically detect the polarization degree of incoming light using spin filtering of photoinduced spin-polarized electron currents. Our structure is a pin diode with a single GaAs quantum well as active region and a Fe∕Tb multilayer on top of a MgO tunnel barrier as n-contact where the spin-polarized electron current is filtered. The photocurrent depends on the magnetization of the contacts and on the polarization of the injected light. We prove that even in remanence and at room temperature the degree of circular polarization of the incident light can be unambiguously determined by the photocurrent intensity.
We present phase coherence time measurements in quasi-one-dimensional mesoscopic wires made from high mobility two-dimensional electron gas. By implanting gallium ions into a GaAs/AlGaAs heterojunction we are able to vary the diffusion coefficient over 2 orders of magnitude. We show that in the diffusive limit, the decoherence time follows a power law as a function of diffusion coefficient as expected by theory. When the disorder is low enough so that the samples are semiballistic, we observe a new and unexpected regime in which the phase coherence time is independent of disorder. In addition, for all samples the temperature dependence of the phase coherence time follows a power law down to the lowest temperatures without any sign of saturation and this strongly suggests that the frequently observed low temperature saturation is not intrinsic.
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