PMID- 15677557
OWN - NLM
STAT- MEDLINE
DCOM- 20050607
LR  - 20220408
IS  - 0006-4971 (Print)
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 10
DP  - 2005 May 15
TI  - Overexpression of transcripts originating from the MMSET locus characterizes all 
      t(4;14)(p16;q32)-positive multiple myeloma patients.
PG  - 4060-9
AB  - Multiple myeloma (MM) is a B-lineage malignancy characterized by diverse genetic 
      subtypes and clinical outcomes. The recurrent immunoglobulin heavy chain (IgH) 
      switch translocation, t(4;14)(p16;q32), is associated with poor outcome, though 
      the mechanism is unclear. Quantitative reverse-transcription-polymerase chain 
      reaction (RT-PCR) for proposed target genes on a panel of myeloma cell lines and 
      purified plasma cells showed that only transcripts originating from the 
      WHSC1/MMSET/NSD2 gene are uniformly dysregulated in all t(4;14)POS patients. The 
      different transcripts detected, multiple myeloma SET domain containing protein 
      (MMSET I), MMSET II, Exon 4a/MMSET III, and response element II binding protein 
      (RE-IIBP), are produced by alternative splicing and alternative transcription 
      initiation events. Translation of the various transcripts, including those from 
      major breakpoint region 4-2 (MB4-2) and MB4-3 breakpoint variants, was confirmed 
      by transient transfection and immunoblotting. Green fluorescent protein 
      (GFP)-tagged MMSET I and II, corresponding to proteins expressed in MB4-1 
      patients, localized to the nucleus but not nucleoli, whereas the MB4-2 and MB4-3 
      proteins concentrate in nucleoli. Cloning and localization of the Exon 4a/MMSET 
      III splice variant, which contains the protein segment lost in the MB4-2 variant, 
      identified a novel protein domain that prevents nucleolar localization. Kinetic 
      studies using photobleaching suggest that the breakpoint variants are 
      functionally distinct from wild-type proteins. In contrast, RE-IIBP is 
      universally dysregulated and also potentially functional in all t(4;14)POS 
      patients irrespective of fibroblast growth factor receptor 3 (FGFR3) expression 
      or breakpoint type.
FAU - Keats, Jonathan J
AU  - Keats JJ
AD  - Department of Oncology, University of Alberta & Cross Cancer Institute, 11560 
      University Ave, Edmonton, AB, T6G 1Z2, Canada.
FAU - Maxwell, Christopher A
AU  - Maxwell CA
FAU - Taylor, Brian J
AU  - Taylor BJ
FAU - Hendzel, Michael J
AU  - Hendzel MJ
FAU - Chesi, Marta
AU  - Chesi M
FAU - Bergsagel, P Leif
AU  - Bergsagel PL
FAU - Larratt, Loree M
AU  - Larratt LM
FAU - Mant, Michael J
AU  - Mant MJ
FAU - Reiman, Tony
AU  - Reiman T
FAU - Belch, Andrew R
AU  - Belch AR
FAU - Pilarski, Linda M
AU  - Pilarski LM
LA  - eng
GR  - CA80963/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, P.H.S.
DEP - 20050127
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Carrier Proteins)
RN  - 0 (Repressor Proteins)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 2.1.1.43 (NSD2 protein, human)
SB  - IM
MH  - Carrier Proteins/*genetics/metabolism
MH  - Chromosomes, Human, Pair 14/*genetics
MH  - Chromosomes, Human, Pair 4/*genetics
MH  - Gene Expression Regulation, Neoplastic/*genetics
MH  - Histone-Lysine N-Methyltransferase
MH  - Humans
MH  - Kinetics
MH  - Multiple Myeloma/*genetics/metabolism/pathology
MH  - Repressor Proteins/*genetics/metabolism
MH  - Survival Rate
MH  - Transcription, Genetic/*genetics
MH  - Translocation, Genetic/*genetics
MH  - Tumor Cells, Cultured
PMC - PMC1895072
EDAT- 2005/01/29 09:00
MHDA- 2005/06/09 09:00
PMCR- 2006/05/15
CRDT- 2005/01/29 09:00
PHST- 2005/01/29 09:00 [pubmed]
PHST- 2005/06/09 09:00 [medline]
PHST- 2005/01/29 09:00 [entrez]
PHST- 2006/05/15 00:00 [pmc-release]
AID - S0006-4971(20)45498-9 [pii]
AID - 01054060 [pii]
AID - 10.1182/blood-2004-09-3704 [doi]
PST - ppublish
SO  - Blood. 2005 May 15;105(10):4060-9. doi: 10.1182/blood-2004-09-3704. Epub 2005 Jan 
      27.