The genetic architecture of multiple myeloma
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TLDR
The following review provides a comprehensive coverage of the genetic and epigenetic events contributing to the initiation and progression of multiple myeloma and where possible these abnormalities have been linked to disease prognosis.Abstract:
Multiple myeloma is a malignant proliferation of monoclonal plasma cells leading to clinical features that include hypercalcaemia, renal dysfunction, anaemia, and bone disease (frequently referred to by the acronym CRAB) which represent evidence of end organ failure. Recent evidence has revealed myeloma to be a highly heterogeneous disease composed of multiple molecularly-defined subtypes each with varying clinicopathological features and disease outcomes. The major division within myeloma is between hyperdiploid and nonhyperdiploid subtypes. In this division, hyperdiploid myeloma is characterised by trisomies of certain odd numbered chromosomes, namely, 3, 5, 7, 9, 11, 15, 19, and 21 whereas nonhyperdiploid myeloma is characterised by translocations of the immunoglobulin heavy chain alleles at chromosome 14q32 with various partner chromosomes, the most important of which being 4, 6, 11, 16, and 20. Hyperdiploid and nonhyperdiploid changes appear to represent early or even initiating mutagenic events that are subsequently followed by secondary aberrations including copy number abnormalities, additional translocations, mutations, and epigenetic modifications which lead to plasma cell immortalisation and disease progression. The following review provides a comprehensive coverage of the genetic and epigenetic events contributing to the initiation and progression of multiple myeloma and where possible these abnormalities have been linked to disease prognosis.read more
Citations
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Journal ArticleDOI
Heterogeneity of genomic evolution and mutational profiles in multiple myeloma
Niccolo Bolli,Hervé Avet-Loiseau,David C. Wedge,Peter Van Loo,Ludmil B. Alexandrov,Inigo Martincorena,Kevin J. Dawson,Francesco Iorio,Serena Nik-Zainal,Graham R. Bignell,Jonathan Hinton,Yang Li,Jose M. C. Tubio,Stuart McLaren,Sarah O' Meara,Adam Butler,Jon W. Teague,Laura Mudie,Elizabeth Anderson,Naim U. Rashid,Yu-Tzu Tai,Masood A. Shammas,Adam S. Sperling,Mariateresa Fulciniti,Paul G. Richardson,Giovanni Parmigiani,Florence Magrangeas,Stephane Minvielle,Philippe Moreau,Michel Attal,Thierry Facon,P. Andrew Futreal,Kenneth C. Anderson,Peter J. Campbell,Nikhil C. Munshi +34 more
TL;DR: The myeloma genome is heterogeneous across the cohort, and exhibits diversity in clonal admixture and in dynamics of evolution, which may impact prognostic stratification, therapeutic approaches and assessment of disease response to treatment.
Journal ArticleDOI
Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group
Pieter Sonneveld,Hervé Avet-Loiseau,Sagar Lonial,Saad Z. Usmani,David S. Siegel,Kenneth C. Anderson,Wee Joo Chng,Philippe Moreau,Michel Attal,Robert A. Kyle,Jo Caers,Jens Hillengass,Jesús F. San Miguel,Niels W.C.J. van de Donk,Hermann Einsele,Joan Bladé,Brian G.M. Durie,Hartmut Goldschmidt,Maria-Victoria Mateos,Antonio Palumbo,Robert Z. Orlowski +20 more
TL;DR: Based on data available today, bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival, and overall survival in t(4;14) and del(17/17p), whereas lenalidomide may be associated with improved progression-based survival and progression- free survival int( 4;14), del( 17/17 p), and t(14;16), and gain(1q).
Journal ArticleDOI
Mutational Spectrum, Copy Number Changes, and Outcome: Results of a Sequencing Study of Patients With Newly Diagnosed Myeloma
Brian A Walker,Eileen M Boyle,Christopher P. Wardell,Alex Murison,Dil B Begum,Nasrin M. Dahir,Paula Proszek,David W. Johnson,Martin Kaiser,Lorenzo Melchor,Lauren I. Aronson,Matthew Scales,Charlotte Pawlyn,Fabio Mirabella,John R Jones,Annamaria Brioli,Aneta Mikulasova,David A Cairns,Walter M Gregory,Ana Quartilho,Mark T. Drayson,Nigel H. Russell,Gordon Cook,Graham Jackson,Xavier Leleu,Faith E. Davies,Gareth J. Morgan +26 more
TL;DR: The understanding of genetic events in myeloma is refined and clinically relevant mutations that may be used to better stratify patients at presentation are identified to generate an international staging system mutation score that can identify a high-risk population of patients who experience relapse and die prematurely.
Journal ArticleDOI
Genomic complexity of multiple myeloma and its clinical implications
Salomon Manier,Karma Salem,Karma Salem,Jihye Park,Jihye Park,Dan A. Landau,Gad Getz,Irene M. Ghobrial,Irene M. Ghobrial +8 more
TL;DR: This Review describes the 'driver' gene alterations involved in the development and progression of MM, with a focus on the sequential acquisition of the main genomic aberrations and provides valuable insight into the clonal heterogeneity and clonal evolution of the disease.
References
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Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group
Robert A. Kyle,J. Anthony Child,Kenneth C. Anderson,Bart Barlogie,Régis Bataille,William I. Bensinger,Joan Bladé,Mario Boccadoro,William S. Dalton,Meletios A. Dimopoulos,Benjamin Djulbegovic,Mark T. Drayson,Brian G.M. Durie,Thiery Facon,Rafael Fonseca,Gösta Gahrton,Philip R. Greipp,Jean Luc Harousseau,David P. Harrington,Mohamad A. Hussein,Douglas E. Joshua,Heinz Ludwig,Gareth J. Morgan,Martin M. Oken,R. L. Powles,Paul G. Richardson,David Roodman,Jesús F. San Miguel,Kazuyuki Shimizu,Chaim Shustik,Bhawna Sirohi,Pieter Sonneveld,Guido J Tricot,Ingemar Turesson,Brian G Van Ness,David H. Vesole,Donna M. Weber,Jan Westin,Keith Wheatley +38 more
TL;DR: The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations to facilitate comparison of therapeutic trial data.
Journal ArticleDOI
Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
Jesús F. San Miguel,Rudolf Schlag,Nuriet K. Khuageva,Meletios A. Dimopoulos,Ofer Shpilberg,Martin Kropff,Ivan Spicka,Maria Teresa Petrucci,Antonio Palumbo,Olga Samoilova,Anna Dmoszynska,Kudrat Abdulkadyrov,Rik Schots,Bin Jiang,Maria-Victoria Mateos,Kenneth C. Anderson,Dixie Lee Esseltine,Kevin Liu,Andrew Cakana,Helgi van de Velde,Paul G. Richardson +20 more
TL;DR: Bortezomib plus melphalan-prednisone alone in patients with newly diagnosed myeloma who were ineligible for high-dose therapy was superior to melphAlan-predisonsone alone.
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