SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status

Leukemia
Lucía López-CorralNorma C Gutiérrez

Abstract

Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P=0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P=0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.

References

Jun 12, 1980·The New England Journal of Medicine·R A Kyle, P R Greipp
Apr 29, 1998·Genes, Chromosomes & Cancer·O MonniS Knuutila
Aug 10, 2000·The American Journal of Pathology·S KnuutilaY Aalto
Dec 7, 2000·Molecular Cell·J B WeitzmanM Yaniv
Feb 22, 2002·The New England Journal of Medicine·Robert A KyleL Joseph Melton
Oct 19, 2005·Cancer Letters·Thomas W Glover
Oct 26, 2005·Cancer Letters·Louise V O'Keefe, Robert I Richards
Jun 15, 2007·Human Molecular Genetics·Kim Debacker, R Frank Kooy
Jun 22, 2007·The New England Journal of Medicine·Robert A KyleS Vincent Rajkumar
Aug 19, 2007·Cancer Cell·Jonathan J KeatsP Leif Bergsagel
Sep 25, 2008·Nature Reviews. Cancer·Ricky W JohnstoneMark J Smyth
Oct 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Paola E LeoneGareth J Morgan
Feb 3, 2009·British Journal of Haematology·Michel JourdanBernard Klein
Feb 24, 2009·Blood·Brendan M WeissW Michael Kuehl
Mar 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Stephan MathasBernd Dörken
Mar 11, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nicholas J DickensGareth J Morgan
Aug 21, 2010·Nature·Shinichiro NakadaDaniel Durocher
Feb 3, 2011·Current Genomics·Laura W DillonYuh-Hwa Wang
Feb 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lucía López-CorralJesús F San Miguel
Mar 25, 2011·Nature·Michael A ChapmanTodd R Golub
Jun 15, 2011·Journal of Neuropathology and Experimental Neurology·Brent A OrrCharles G Eberhart
Jun 18, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Hutton M KearneyUNKNOWN Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee
Sep 16, 2011·The Journal of Biological Chemistry·Hao GengDavid Z Qian
Oct 4, 2011·Genes, Chromosomes & Cancer·Iona ChengJohn S Witte

❮ Previous
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Citations

Apr 12, 2013·Leukemia·S Kumar, S V Rajkumar
May 23, 2015·Expert Opinion on Orphan Drugs·Karma Z Salem, Irene M Ghobrial
Dec 17, 2015·Blood·Bruno PaivaUNKNOWN Spanish Myeloma Group / Program Study and Treatment of Hematological Malignancies cooperative study groups
Jul 19, 2013·American Journal of Hematology·Stéphanie PoulainXavier Leleu
Jul 30, 2014·Clinical Lymphoma, Myeloma & Leukemia·Noopur RajeUNKNOWN Managing Myeloma Continuing Education Initiative Advisory Group
Oct 10, 2014·Blood·Irene M Ghobrial, Ola Landgren
Feb 20, 2015·Hematology·Jesus San Miguel
May 11, 2016·International Journal of Laboratory Hematology·N W C J van de DonkS Zweegman
May 7, 2016·Genes, Chromosomes & Cancer·Merav LeibaLuba Trakhtenbrot
Nov 9, 2016·Best Practice & Research. Clinical Haematology·Ramón García-SanzMartín Pérez-Andrés
Nov 1, 2016·Expert Review of Hematology·Antonino NeriPellegrino Musto
May 10, 2016·European Journal of Haematology·Aneta MikulasovaPetr Kuglik
Nov 26, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Inhye E AhnOla Landgren
Aug 5, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonio PalumboPhilippe Moreau
Apr 14, 2016·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·P SeggesA Maiolino
Jan 10, 2018·Nature Reviews. Clinical Oncology·Irene M GhobrialDavid P Steensma
May 17, 2018·British Journal of Haematology·Jeffrey A Zonder
Feb 23, 2018·Leukemia·K K JovanovićS Manier
Apr 23, 2015·Scientific Reports·Jun IshikawaTakashi Tsuji
Apr 24, 2019·Blood·Tarek H MouhieddineIrene M Ghobrial
Jun 2, 2016·American Society of Clinical Oncology Educational Book·Salomon ManierIrene M Ghobrial
Jan 30, 2020·PloS One·Natasha FriendAndrew C W Zannettino
Jan 3, 2020·Current Opinion in Oncology·Oliver C LomasIrene M Ghobrial

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