|
Multiple Myeloma
|
0.100 |
Biomarker
|
disease |
BEFREE |
14q32 (IgH) translocations are highly prevalent in both sPCL and pPCL (82-87%); in pPCL IgH translocations almost exclusively involve 11q13 (CCND1), supporting a central etiological role, while in sPCL multiple partner oncogenes are involved, including 11q13, 4p16 (FGFR3/MMSET) and 16q23 (MAF), recapitulating MM.
|
18216867 |
2008 |
|
Multiple Myeloma
|
0.100 |
Biomarker
|
disease |
BEFREE |
NSD2 is recruited through its PHD domain to oncogenic gene loci to drive multiple myeloma.
|
23980095 |
2013 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
WHSC1, a 90 kb SET domain-containing gene, expressed in early development and homologous to a Drosophila dysmorphy gene maps in the Wolf-Hirschhorn syndrome critical region and is fused to IgH in t(4;14) multiple myeloma.
|
9618163 |
1998 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
A number of non-t(4;14) cases also express MMSET consistent with this gene playing a role in myeloma pathogenesis.
|
15355895 |
2004 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript.
|
12433679 |
2003 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
LHGDN |
A subset of multiple myeloma harboring the t(4;14)(p16;q32) translocation lacks FGFR3 expression but maintains an IGH/MMSET fusion transcript.
|
12433679 |
2003 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Although a poor prognosis is linked with elevated MMSET expression, an extended follow-up period will be required to evaluate the significance of elevated TACC3 and p21 expression in this subgroup of MM.
|
15198734 |
2004 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Although all MM tumors and cell lines with a t(4;14) translocation have dysregulated MMSET, about 25% do not express FGFR3.
|
20393505 |
2010 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Although several key molecular events in disease initiation or progression have been confirmed (eg, FGFR3/MMSET activation) or implicated (eg, chromosome 13 deletion), the mechanisms of MM development remain enigmatic.
|
12731663 |
2003 |
|
Multiple Myeloma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Although studies have shown the involvement of MMSET/Wolf-Hirschhorn syndrome candidate 1 in development, its mode of action in the pathogenesis of MM is largely unknown.
|
20974671 |
2011 |
|
Multiple Myeloma
|
0.100 |
Biomarker
|
disease |
BEFREE |
As a part of these translational efforts, novel drugs that inhibit oncogenic proteins overexpressed in defined molecular subgroups of the disease, such as FGFR3 and MMSET in t(4;14) MM, are currently being developed.
|
23233602 |
2012 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
By using genetically matched MM cell lines that had either high (pathological) or low (physiological) expression of MMSET, we found that MMSET-high cells had increased damage at baseline.
|
27109101 |
2016 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Collectively, these data suggest that, by acting directly as a modifier of chromatin as well as through binding of other chromatin-modifying enzymes, MMSET influences gene expression and potentially acts as a pathogenic agent in multiple myeloma.
|
18156491 |
2008 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
LHGDN |
Collectively, these data suggest that, by acting directly as a modifier of chromatin as well as through binding of other chromatin-modifying enzymes, MMSET influences gene expression and potentially acts as a pathogenic agent in multiple myeloma.
|
18156491 |
2008 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Dramatic overexpression of NSD2 in t(4;14) multiple myeloma (MM) and an activating mutation of NSD2 discovered in acute lymphoblastic leukemia are significantly associated with altered gene activation, transcription, and DNA damage repair.
|
31248990 |
2019 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
FGFR3/MMSET activation) or implicated (e.g. chromosome 13 deletion), the mechanisms of MM development remain enigmatic.
|
12846813 |
2003 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
From a clinical standpoint, it is critical to identify MM patients carrying the t(4;14) translocation, which is present in 15% of myelomas and is associated with dysregulation of WHSC1/MMSET and often FGFR3.
|
22160056 |
2011 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Histone lysine methyltransferase NSD2 was frequently overexpressed in multiple types of cancer such as multiple myeloma, stomach and colon cancer, and the overexpression of it usually associated with aggressiveness tumor type.
|
28338204 |
2017 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
IGH-MMSET transcripts were found in 11 of the 53 (20%) MM cases and 1 of 16 (6%) cases of monoclonal gammopathy of uncertain significance.
|
10945609 |
2000 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In particular, MMSET/NSD2 selective inhibition is being pursued for therapeutic interventions against multiple myeloma (MM) cases, especially in multiple myeloma t(4;14)(p16.3;q32) translocation that is associated with a significantly worse prognosis than other MM subgroups.
|
30471851 |
2019 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
In studies of patients with multiple myeloma (MM), gene expression profiling (GEP) of myeloma cells demonstrates substantially higher expression of MMSET, FGFR3, CCND3, CCND1, MAF, and MAFB--the partner genes of 14q32 translocations--than GEP of plasma cells from healthy individuals.
|
24638926 |
2014 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
In t(4;14) MM, the MM SET domain (MMSET) protein is universally overexpressed and has been suggested to have an important tumorigenic role.
|
26196464 |
2015 |
|
Multiple Myeloma
|
0.100 |
AlteredExpression
|
disease |
BEFREE |
Markedly increased MMSET expression was found in 1 MM showing associated FGFR3 and MMSET signals on an unidentified chromosome.
|
15543617 |
2005 |
|
Multiple Myeloma
|
0.100 |
GeneticVariation
|
disease |
BEFREE |
Nearly 40% of MM tumors have immunoglobulin H (IgH) translocations involving four recurrent chromosomal loci (oncogenes): 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (MMSET and FGFR3), and 16q23 (c-maf).
|
12846810 |
2003 |
|
Multiple Myeloma
|
0.100 |
Biomarker
|
disease |
BEFREE |
Nearly half of these tumors are nonhyperdiploid and mostly have immunoglobulin H (IgH) translocations that involve 5 recurrent chromosomal loci, including 11q13 (cyclin D1), 6p21 (cyclin D3), 4p16 (fibroblast growth factor receptor 3 [FGFR3] and multiple myeloma SET domain [MMSET]), 16q23 (c-maf), and 20q11 (mafB).
|
15090448 |
2004 |