Impact of Genes Highly Correlated with MMSET Myeloma on the Survival of Non-MMSET Myeloma Patients

Details

• Personal Author:
  Ahn IE ; Landgren O ; Mailankody S ; Morgan G ; Munshi NC ; Pfeiffer RM ; Sonneveld P ; van Duin M ; Walker BA ; Wu SP
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Blood Diagnosis Genetics Health Care Facilities Workforce And Services Immune System Neoplasms Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Analytical Models Biological Factors Blood Cells Bone Marrow Cancer Cell Alteration Clinical Diagnosis Deoxyribonucleic Acids DNA DNA Damage DNA Microarrays Gene Expression Gene Regulation Genes Hematopoietic System Humans Immunoglobulins Medical Monitoring Medical Records Mutation Myeloid Tissue Oncogenesis Regression Analysis Risk Factors Survival Rate Therapeutic Agents

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• ISSN:
  1078-0432
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Arkansas ; Maryland ; Massachusetts ; New York ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 6
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  22
• Issue:
  16
• NIOSHTIC Number:
  nn:20050747
• Citation:
  Clin Cancer Res 2016 Aug; 22(16):4039-4044
• Contact Point Address:
  Ola Landgren, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
• Email:
  landgrec@mskcc.org
• Federal Fiscal Year:
  2016
• Performing Organization:
  Albert Einstein College of Medicine, Inc., Bronx, New York
• Peer Reviewed:
  True
• Start Date:
  20170701
• Source Full Name:
  Clinical Cancer Research
• End Date:
  20200630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ba19c34f26db739a1d874189dd05b80f190045d2f897205ae59dd2bd96d20f6a5dab766d31caf8a3b3b66bd015c667658ef22641b19a225af202e28fd13fd467
• Download URL:
  https://stacks.cdc.gov/view/cdc/210971/cdc_210971_DS1.pdf
• File Type:
  [PDF - 464.99 KB ]