title: Impact of Genes Highly Correlated with MMSET Myeloma on the Survival of Non-MMSET Myeloma Patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Multiple Myeloma Section, NCI, NIH, Bethesda, Maryland.
authors: S Peter
authors: SP
authors: Wu
authors: Department of Cancer Epidemiology and Genetics, Biostatistics Branch, NCI, NIH, Rockville, Maryland.
authors: Ruth M
authors: RM
authors: Pfeiffer
authors: Multiple Myeloma Section, NCI, NIH, Bethesda, Maryland.
authors: Inhye E
authors: IE
authors: Ahn
authors: Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Sham
authors: S
authors: Mailankody
authors: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Pieter
authors: P
authors: Sonneveld
authors: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors: Mark
authors: M
authors: van Duin
authors: Lebow Institute of Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors: Nikhil C
authors: NC
authors: Munshi
authors: Section of Haemato-Oncology, The Institute of Cancer Research, London, United Kingdom.
authors: Brian A
authors: BA
authors: Walker
authors: Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors: Gareth
authors: G
authors: Morgan
authors: Myeloma Service, Memorial Sloan Kettering Cancer Center, New York, New York. landgrec@mskcc.org.
authors: Ola
authors: O
authors: Landgren
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012097:Repressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human