TY - JOUR A1 - Williams, Richard D. A1 - Chagtai, Tasnim A1 - Alcaide-German, Marisa A1 - Apps, John A1 - Wegert, Jenny A1 - Popov, Sergey A1 - Vujanic, Gordan A1 - Van Tinteren, Harm A1 - Van den Heuvel-Eibrink, Marry M A1 - Kool, Marcel A1 - De Kraker, Jan A1 - Gisselsson, David A1 - Graf, Norbert A1 - Gessler, Manfred A1 - Pritchard-Jones, Kathy T1 - Multiple mechanisms of MYCN dysregulation in Wilms tumour JF - Oncotarget N2 - Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies. We describe parallel evolution of genomic copy number gain and point mutation of MYCN in the contralateral tumours of a remarkable bilateral case in which independent contralateral mutations of TP53 also evolve over time. We report a second bilateral case in which MYCN gain is a germline aberration. Our results suggest a significant role for MYCN dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN gain is prognostically significant, and suggest that the novel P44L somatic variant is likely to be an activating mutation. KW - integrative genomics viewer KW - oncogene amplification KW - sequencing data KW - gene KW - gain KW - copy number KW - somatic mutations KW - beta-catenin KW - histology KW - reveals KW - Wilms tumour KW - MYCN KW - DNA methylation KW - prognostic marker Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143471 VL - 6 IS - 9 ER - TY - JOUR A1 - Hopfmann, C. A1 - Albert, F. A1 - Schneider, C. A1 - Höfling, S. A1 - Kamp, M. A1 - Forchel, A. A1 - Kanter, I. A1 - Reizenstein, S. T1 - Nonlinear emission characteristics of quantum dot-micropillar lasers in the presence of polarized optical feedback JF - New Journal of Physics N2 - We report on electrically pumped quantum dot-microlasers in the presence of polarized self-feedback. The high-\(\beta\) microlasers show two orthogonal, linearly polarized emission modes which are coupled via the common gain medium. This coupling is explained in terms of gain competition between the two lasing modes and leads to distinct differences in their input-output characteristics. By applying polarized self-feedback via an external mirror, we are able to control the laser characteristics of the emission modes in terms of the output power, the coherence time and the photon statistics. We find that linearly polarized self-feedback stabilizes the lasing of a given mode, while cross-polarized feedback between the two modes reduces strongly the intensity of the other emission mode showing particular high-intensity fluctuations and even super-thermal values of the photon autocorrelation function \(g^{(2)} (\tau)\) at zero delay. Measurements of \(g^{(2)} (\tau)\) under external feedback also allow us to detect revival peaks associated with the round trip time of the external cavity. Analyzing the damping and shape of the \(g^{(2)} (\tau)\) revival peaks by a phenomenological model provides us insight into the underlying physics such as the effective exciton lifetime and gain characteristics of the quantum dots in the active region of these microlasers. KW - semiconductor lasers KW - coherence KW - system KW - gain Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123127 SN - 1367-2630 VL - 15 IS - 025030 ER -