Impact of genes highly correlated with MMSET myeloma on the survival of non-MMSET myeloma patients Journal Article
| Authors: | Wu, S. P.; Pfeiffer, R. M.; Ahn, I. E.; Mailankody, S.; Sonneveld, P.; Duin, M. V.; Munshi, N. C.; Walker, B. A.; Morgan, G.; Landgren, O. |
| Article Title: | Impact of genes highly correlated with MMSET myeloma on the survival of non-MMSET myeloma patients |
| Abstract: | Purpose: The poor prognosis of multiple myeloma with t(4;14) is driven by the fusion of genes encoding multiple myeloma SET domain (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 that correlated most with MMSET myeloma were selected on the basis of a multivariable linear regression and Bonferroni correction and refined on the basis of 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 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. Conclusions: MMSET-like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype. © 2016 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 22 |
| Issue: | 16 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2016-08-01 |
| Start Page: | 4039 |
| End Page: | 4044 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-15-2366 |
| PROVIDER: | scopus |
| PUBMED: | 26847058 |
| PMCID: | PMC5576175 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2016 -- Source: Scopus |
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