PMID- 30914633
OWN - NLM
STAT- MEDLINE
DCOM- 20200203
LR  - 20210109
IS  - 2044-5385 (Electronic)
IS  - 2044-5385 (Linking)
VI  - 9
IP  - 4
DP  - 2019 Mar 26
TI  - Deciphering the chronology of copy number alterations in Multiple Myeloma.
PG  - 39
LID - 10.1038/s41408-019-0199-3 [doi]
LID - 39
AB  - Multiple myeloma (MM) and its precursor condition MGUS are characterized by 
      chromosomal aberrations. Here, we comprehensively characterize the order of 
      occurrence of these complex genomic events underlying MM development using 500 
      MGUS, and MM samples. We identify hyperdiploid MM (HMM) and non-HMM as 
      genomically distinct entities with different evolution of the copy number 
      alterations. In HMM, gains of 9,15 or 19 are the first and clonal events observed 
      as clonal even at MGUS stage. These events are thus early and may underlie 
      initial transformation of normal plasma cells to MGUS cells. However, CNAs may 
      not be adequate for progression to MM except in 15% of the patients in whom the 
      complex subclonal deletion events are observed in MM but not MGUS. In NHMM, 
      besides the driver translocations, clonal deletion of 13 and 1q gain are early 
      events also observed in MGUS. We combined this information to propose a timeline 
      for copy number alteration.
FAU - Aktas Samur, Anil
AU  - Aktas Samur A
AD  - Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA, 02215, 
      USA.
AD  - Department of Biostatistics, Harvard T.H. Chan School of Public Health Boston, 
      Boston, MA, 02115, USA.
FAU - Minvielle, Stephane
AU  - Minvielle S
AD  - Inserm UMR892, CNRS 6299, Universite de Nantes; Centre Hospitalier Universitaire 
      de Nantes, Unite Mixte de Genomique du Cancer, Nantes, France.
FAU - Shammas, Masood
AU  - Shammas M
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02115, USA.
AD  - VA Boston Healthcare System, Boston, MA, 02115, USA.
FAU - Fulciniti, Mariateresa
AU  - Fulciniti M
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02115, USA.
FAU - Magrangeas, Florence
AU  - Magrangeas F
AD  - Inserm UMR892, CNRS 6299, Universite de Nantes; Centre Hospitalier Universitaire 
      de Nantes, Unite Mixte de Genomique du Cancer, Nantes, France.
FAU - Richardson, Paul G
AU  - Richardson PG
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02115, USA.
FAU - Moreau, Philippe
AU  - Moreau P
AD  - Inserm UMR892, CNRS 6299, Universite de Nantes; Centre Hospitalier Universitaire 
      de Nantes, Unite Mixte de Genomique du Cancer, Nantes, France.
FAU - Attal, Michel
AU  - Attal M
AD  - University Cancer Center of Toulouse Institut National de la Sante, Toulouse, 
      France.
FAU - Anderson, Kenneth C
AU  - Anderson KC
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02115, USA.
FAU - Parmigiani, Giovanni
AU  - Parmigiani G
AD  - Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA, 02215, 
      USA.
AD  - Department of Biostatistics, Harvard T.H. Chan School of Public Health Boston, 
      Boston, MA, 02115, USA.
FAU - Avet-Loiseau, Herve
AU  - Avet-Loiseau H
AD  - University Cancer Center of Toulouse Institut National de la Sante, Toulouse, 
      France. avet-loiseau.h@chu-toulouse.fr.
AD  - Unite de Genomique du Myelome, IUC-Oncopole 2 Avenue Hubert Curien Cedex 1, 
      Toulouse, 31037, France. avet-loiseau.h@chu-toulouse.fr.
FAU - Munshi, Nikhil C
AU  - Munshi NC
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02115, USA. nikhil_munshi@dfci.harvard.edu.
AD  - VA Boston Healthcare System, Boston, MA, 02115, USA. 
      nikhil_munshi@dfci.harvard.edu.
FAU - Samur, Mehmet Kemal
AU  - Samur MK
AD  - Department of Data Sciences, Dana Farber Cancer Institute, Boston, MA, 02215, 
      USA. mehmet_samur@dfci.harvard.edu.
AD  - Department of Biostatistics, Harvard T.H. Chan School of Public Health Boston, 
      Boston, MA, 02115, USA. mehmet_samur@dfci.harvard.edu.
AD  - Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, 02115, USA. mehmet_samur@dfci.harvard.edu.
LA  - eng
GR  - I01 BX001584/BX/BLRD VA/United States
GR  - P01 CA155258/CA/NCI NIH HHS/United States
GR  - P50 CA100707/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190326
PL  - United States
TA  - Blood Cancer J
JT  - Blood cancer journal
JID - 101568469
SB  - IM
MH  - DNA Copy Number Variations/*genetics
MH  - Humans
MH  - Multiple Myeloma/*genetics
PMC - PMC6435669
COIS- The authors declare that they have no conflict of interest.
EDAT- 2019/03/28 06:00
MHDA- 2020/02/06 06:00
PMCR- 2019/03/26
CRDT- 2019/03/28 06:00
PHST- 2019/01/22 00:00 [received]
PHST- 2019/03/12 00:00 [accepted]
PHST- 2019/03/07 00:00 [revised]
PHST- 2019/03/28 06:00 [entrez]
PHST- 2019/03/28 06:00 [pubmed]
PHST- 2020/02/06 06:00 [medline]
PHST- 2019/03/26 00:00 [pmc-release]
AID - 10.1038/s41408-019-0199-3 [pii]
AID - 199 [pii]
AID - 10.1038/s41408-019-0199-3 [doi]
PST - epublish
SO  - Blood Cancer J. 2019 Mar 26;9(4):39. doi: 10.1038/s41408-019-0199-3.