Details:

Alternative Title:
Clin Cancer Res
Personal Author:
Wu, S. Peter ; Pfeiffer, Ruth M. ; Ahn, Inhye E. ; Mailankody, Sham ; Sonneveld, Pieter ; ... More +
Wu, S. Peter ; Pfeiffer, Ruth M. ; Ahn, Inhye E. ; Mailankody, Sham ; Sonneveld, Pieter ; van Duin, Mark ; Munshi, Nikhil ; Walker, Brian ; Morgan, Gareth ; Landgren, Ola Less -
Description:
Purpose

The poor prognosis of multiple myeloma with t(4;14) is driven by the fusion of genes encoding MMSET and immunoglobulin heavy chain. Specific genes affected by MMSET and their clinical implications in Non-MMSET myeloma remain undetermined.

Experimental design

We obtained gene-expression profiles of 1,032 newly diagnosed myeloma patients enrolled in Total Therapy 2, Total Therapy 3, Myeloma IX, and HOVON65-GMMGHD4 trials, and 156 patients from Multiple Myeloma Resource Collection. Probes most correlated with MMSET myeloma were selected based on a multivariable linear regression and Bonferroni correction, and refined based on the strength of association with survival in Non-MMSET patients.

Results

Ten MMSET-like probes were associated with poor survival in Non-MMSET myeloma. Non-MMSET myeloma patients in the highest quartile of the 10-gene signature (MMSET-like myeloma) had 5-year overall survival similar to that of MMSET myeloma (highest quartile vs. lowest quartile hazard ratio [HR]=2.0, 95% confidence interval [CI] 1.5-2.8 in MMSET-like myeloma; HR=2.3, 95% CI: 1.6-3.3 in MMSET myeloma). Analyses of MMSET-like gene signature suggested the involvement of p53 and MYC pathways.

Conclusion

MMSET-like gene signature captures a subset of high-risk myeloma patients under-represented by conventional risk stratification platforms, and defines a distinct biological subtype.


Subjects:
[+]
Article CDNA Microarray High Risk Myeloma MMSET Multiple Myeloma T(4;14)
Source:
Clin Cancer Res. 22(16):4039-4044.
Pubmed ID:
26847058
Pubmed Central ID:
PMC5576175
Document Type:
Journal Article
Funding:
U01 FD005642/FD/FDA HHS/United States ; U01 OH011475/OH/NIOSH CDC HHS/United States
U01 FD005642/FD/FDA HHS/United States ; U01 OH011475/OH/NIOSH CDC HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:0f8e12b2ea20e972985759302b76ac3d85c199621be38f7c523535c86afb2aa6
Download URL:
https://stacks.cdc.gov/view/cdc/47868/cdc_47868_DS1.pdf
File Type:

Supporting Files

• 	NIHMS757967-supplement-1.docx	docx
  	nihms757967.nxml	bin
  	nihms757967f1.gif	gif
  	nihms757967f1.jpg	jpeg

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