TY - JOUR A1 - Mitchell, Jonathan S. A1 - Li, Ni A1 - Weinhold, Niels A1 - Försti, Asta A1 - Ali, Mina A1 - van Duin, Mark A1 - Thorleifsson, Gudmar A1 - Johnson, David C. A1 - Chen, Bowang A1 - Halvarsson, Britt-Marie A1 - Gudbjartsson, Daniel F. A1 - Kuiper, Rowan A1 - Stephens, Owen W. A1 - Bertsch, Uta A1 - Broderick, Peter A1 - Campo, Chiara A1 - Einsele, Hermann A1 - Gregory, Walter A. A1 - Gullberg, Urban A1 - Henrion, Marc A1 - Hillengass, Jens A1 - Hoffmann, Per A1 - Jackson, Graham H. A1 - Johnsson, Ellinor A1 - Jöud, Magnus A1 - Kristinsson, Sigurdur Y. A1 - Lenhoff, Stig A1 - Lenive, Oleg A1 - Mellqvist, Ulf-Henrik A1 - Migliorini, Gabriele A1 - Nahi, Hareth A1 - Nelander, Sven A1 - Nickel, Jolanta A1 - Nöthen, Markus M. A1 - Rafnar, Thorunn A1 - Ross, Fiona M. A1 - da Silva Filho, Miguel Inacio A1 - Swaminathan, Bhairavi A1 - Thomsen, Hauke A1 - Turesson, Ingemar A1 - Vangsted, Annette A1 - Vogel, Ulla A1 - Waage, Anders A1 - Walker, Brian A. A1 - Wihlborg, Anna-Karin A1 - Broyl, Annemiek A1 - Davies, Faith E. A1 - Thorsteinsdottir, Unnur A1 - Langer, Christian A1 - Hansson, Markus A1 - Kaiser, Martin A1 - Sonneveld, Pieter A1 - Stefansson, Kari A1 - Morgan, Gareth J. A1 - Goldschmidt, Hartmut A1 - Hemminki, Kari A1 - Nilsson, Björn A1 - Houlston, Richard S. T1 - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma JF - Nature Communications N2 - Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development. KW - Cancer genetics KW - Genome-wide association studies KW - Myeloma Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165983 VL - 7 ER - TY - JOUR A1 - Rasche, Leo A1 - Kumar, Manoj A1 - Gershner, Grant A1 - Samant, Rohan A1 - Van Hemert, Rudy A1 - Heidemeier, Anke A1 - Lapa, Constantin A1 - Bley, Thorsten A1 - Buck, Andreas A1 - McDonald, James A1 - Hillengass, Jens A1 - Epstein, Joshua A1 - Thanendrarajan, Sharmilan A1 - Schinke, Carolina A1 - van Rhee, Frits A1 - Zangari, Maurizio A1 - Barlogie, Bart A1 - Davies, Faith E. A1 - Morgan, Gareth J. A1 - Weinhold, Niels T1 - Lack of Spleen Signal on Diffusion Weighted MRI is associated with High Tumor Burden and Poor Prognosis in Multiple Myeloma: A Link to Extramedullary Hematopoiesis? JF - Theranostics N2 - Due to the low frequency of abnormalities affecting the spleen, this organ is often overlooked during radiological examinations. Here, we report on the unexpected finding, that the spleen signal on diffusion-weighted MRI (DW-MRI) is associated with clinical parameters in patients with plasma cell dyscrasias. Methods: We investigated the spleen signal on DW-MRI together with clinical and molecular parameters in 295 transplant-eligible newly diagnosed Multiple Myeloma (NDMM) patients and in 72 cases with monoclonal gammopathy of undetermined significance (MGUS). Results: Usually, the spleen is the abdominal organ with the highest intensities on DW-MRI. Yet, significant signal loss on DW-MRI images was seen in 71 of 295 (24%) NDMM patients. This phenomenon was associated with the level of bone marrow plasmacytosis (P=1x10(-10)) and International Staging System 3 (P=0.0001) but not with gain(1q), and del(17p) or plasma cell gene signatures. The signal was preserved in 72 individuals with monoclonal gammopathy of undetermined significance and generally re-appeared in MM patients responding to treatment, suggesting that lack of signal reflects increased tumor burden. While absence of spleen signal in MM patients with high risk disease defined a subgroup with very poor outcome, re-appearance of the spleen signal after autologous stem cell transplantation was seen in patients with improved outcome. Our preliminary observation suggests that extramedullary hematopoiesis in the spleen is a factor that modifies the DW-MRI signal of this organ. Conclusions: The DW-MRI spleen signal is a promising marker for tumor load and provides prognostic information in MM. KW - multiple myeloma KW - diffusion weighted mri KW - spleen KW - tumor burden KW - high risk KW - extramedullary hematopoiesis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224982 VL - 9 IS - 16 ER - TY - JOUR A1 - Andersen, Jens Peter A1 - Bøgsted, Martin A1 - Dybkær, Karen A1 - Mellqvist, Ulf-Henrik A1 - Morgan, Gareth J. A1 - Goldschmidt, Hartmut A1 - Dimopoulos, Meletios A. A1 - Einsele, Hermann A1 - San Miguel, Jesús A1 - Palumbo, Antonio A1 - Sonneveld, Pieter A1 - Johnsen, Hans Erik T1 - Global myeloma research clusters, output, and citations: a bibliometric mapping and clustering analysis JF - PLoS ONE N2 - Background International collaborative research is a mechanism for improving the development of disease-specific therapies and for improving health at the population level. However, limited data are available to assess the trends in research output related to orphan diseases. Methods and Findings We used bibliometric mapping and clustering methods to illustrate the level of fragmentation in myeloma research and the development of collaborative efforts. Publication data from Thomson Reuters Web of Science were retrieved for 2005-2009 and followed until 2013. We created a database of multiple myeloma publications, and we analysed impact and co-authorship density to identify scientific collaborations, developments, and international key players over time. The global annual publication volume for studies on multiple myeloma increased from 1,144 in 2005 to 1,628 in 2009, which represents a 43% increase. This increase is high compared to the 24% and 14% increases observed for lymphoma and leukaemia. The major proportion (> 90% of publications) was from the US and EU over the study period. The output and impact in terms of citations, identified several successful groups with a large number of intra-cluster collaborations in the US and EU. The US-based myeloma clusters clearly stand out as the most productive and highly cited, and the European Myeloma Network members exhibited a doubling of collaborative publications from 2005 to 2009, still increasing up to 2013. Conclusion and Perspective Multiple myeloma research output has increased substantially in the past decade. The fragmented European myeloma research activities based on national or regional groups are progressing, but they require a broad range of targeted research investments to improve multiple myeloma health care. KW - multiparametric flow cytometry KW - multiple myeloma KW - consensus statement KW - European experts KW - disorders KW - therapy KW - network Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144214 VL - 10 IS - 1 ER -