Impact of Genes Highly Correlated with MMSET Myeloma on the Survival of Non-MMSET Myeloma Patients. Academic Article uri icon

Overview

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. Clin Cancer Res; 22(16); 4039-44. ©2016 AACR.

publication date

  • February 4, 2016

Research

keywords

  • Biomarkers, Tumor
  • Histone-Lysine N-Methyltransferase
  • Multiple Myeloma
  • Repressor Proteins

Identity

PubMed Central ID

  • PMC5576175

Scopus Document Identifier

  • 84982104086

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-15-2366

PubMed ID

  • 26847058

Additional Document Info

volume

  • 22

issue

  • 16