Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma

[Excerpt] Multiple myeloma (MM) is the third most common hematological malignancy, after Non-Hodgkin Lymphoma and Leukemia. MM is generally preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS) [1], and epidemiological studies have identified older age, male gender, family history, and MGUS as risk factors for developing MM [2]. The somatic mutational landscape of sporadic MM has been increasingly investigated, aiming to identify recurrent genetic events involved in myelomagenesis. Whole exome and whole genome sequencing studies have shown that MM is a genetically heterogeneous disease that evolves through accumulation of both clonal and subclonal driver mutations [3] and identified recurrently somatically mutated genes, including KRAS, NRAS, FAM46C, TP53, DIS3, BRAF, TRAF3, CYLD, RB1 and PRDM1 [3,4,5]. Despite the fact that family-based studies have provided data consistent with an inherited genetic susceptibility to MM compatible with Mendelian transmission [6], the molecular basis of inherited MM predisposition is only partly understood. Genome-Wide Association (GWAS) studies have identified and validated 23 loci significantly associated with an increased risk of developing MM that explain ~16% of heritability [7] and only a subset of familial cases are thought to have a polygenic background [8]. Recent studies have identified rare germline variants predisposing to MM in KDM1A [9], ARID1A and USP45 [10], and the implementation of next-generation sequencing technology will allow the characterization of more such rare variants. [...]French National Cancer Institute (INCA) and the Fondation Française pour la Recherche contre le Myélome et les Gammapathies (FFMRG), the Intergroupe Francophone du Myélome (IFM), NCI R01 NCI CA167824 and a generous donation from Matthew Bell. This work was supported in part through the computational resources and staff expertise provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai. Research reported in this paper was supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the Association des Malades du Myélome Multiple (AF3M) for their continued support and participation. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organizatio

LHCb RICH 2 MechanicsNota Interna Pubblica LHCb Collaboration CERN LHCb2000-081 RICH

This note gives an overview of the status of the mechanics for the RICH 2 detector in the LHCb experiment at LHC

LHCb RICH 2 mechanics

This note presents an overview of the status of the mechanics for the RICH 2 detector in the LHCb experiment at LHC

Test-beam results on particle identification with aerogel used as RICH radiator

We present the results obtained by exposing samples of silica aerogel of different thickness and optical properties to pion and proton beams with momenta between 6 and 10 GeV/c in the PS testbeam facility at CERN. Two large diameter pad hybrid photodiodes with 2048 channels, produced at CERN, have been used as photon detectors. Separate Cherenkov rings produced by the different particles were reconstructed obtaining pion/proton separation over the whole momentum range. The number of photoelectrons was measured as a function of aerogel thickness and was found to be in agreement with Monte Carlo expectations. (5 refs)

Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin's lymphoma: Results of the prospective multicenter H96 trial by the GELA/SFGM study group

Purpose: A prospective multicenter trial evaluated a risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation (ASCT) for 245 Hodgkin's lymphoma (HL) patients who experience treatment failure with first-line therapy. Patients and Methods: Poor-risk patients (150 with primary refractory disease or ≥ two of the following risk factors at first relapse: time to relapse < 12 months, stage III or IV at relapse, and relapse within previously irradiated sites) or intermediate-risk patients (95 with one risk factor at relapse) were eligible for tandem or single ASCT, respectively. Results: Among poor-risk patients, 105 (70%), including 30 of 55 with cytoreductive chemotherapy-resistant disease, received tandem ASCT, whereas 92 intermediate-risk patients (97%) received single ASCT. According to intent-to-treat analysis, the 5-year freedom from second failure and overall survival (OS) estimates were 73% and 85%, respectively, for the intermediate-risk group and 46% and 57%, respectively, for the poor-risk group. Outcomes were similar for primary refractory and poor-risk/relapsed HL. For patients with chemotherapy-resistant disease, the 46% 5-year OS rate achieved with tandem ASCT compares favorably with the previously reported 30%. Outcomes for partial and complete responders to cytoreduction receiving tandem ASCT did not differ significantly and were better than those previously reported for partial responders receiving single ASCT, but not superior to those reported for complete responders receiving single ASCT. Six poor-risk patients (4%) died from toxicity. Conclusion: Single ASCT is appropriate for intermediate-risk patients. For poor-risk patients, our results suggest a benefit of tandem ASCT for half of the patients with chemotherapy-resistant disease and partial responders, but not for complete responders to cytoreductive chemotherapy. © 2008 by American Society of Clinical Oncology

A B(4)C silicon target for the detection of neutrino interactions

This note describes the construction of a target for neutrino interactions composed of passive boron carbide plates interleaved with silicon microstrip detectors. The target contains four layers of passive material With a total mass of 45 kg and 600 single-sided silicon microstrip detectors with a total surface of 1.14 m(2) distributed over five layers. It is installed in the NOMAD spectrometer at the CERN SPS neutrino beam. During the 1997 run about 8000v(mu) charged current interactions were estimated to have occurred in the target. For these events it will be possible to perform a precise measurement of both vertex and kinematical variables. This will provide invaluable experience towards the construction of a future large-scale silicon tracker for neutrino oscillation experiments

Performance of long modules of silicon microstrip detectors

This note describes the performance of modules assembled with up to 12 silicon microstrip detectors. These modules were built for the instrumented Silicon Target (STAR) that has been installed in the NOMAD spectrometer. Laboratory and test beam results are compared with model predictions. For a module of nine detectors, test beam results indicate a signal-to-noise ratio of 19, a hit finding efficiency of 99.8% and a spatial resolution of 6.0 μm. Laboratory measurements indicate that modules of twelve detectors exhibit a signal-to-noise ratio of the order of 16