Quantitative analysis of CKS1B mRNA expression and copy number gain in patients with plasma cell disorders

Blood Cells Mol Dis. 2014 Sep;53(3):110-7. doi: 10.1016/j.bcmd.2014.05.006. Epub 2014 Jun 25.

Abstract

In this study, we have examined CKS1B gene expression and copy number in a total of 114- patients at diagnosis: 83 with multiple myeloma (MM) and 31 with monoclonal gammopathy of undetermined significance (MGUS). Results were correlated with cytogenetics, FISH and clinical characteristic. Significant CKS1B mRNA levels in MM compared to MGUS cases (p<0.048) were detected. In MM, the frequency of 1q21 (CKS1B) copy gain was significantly higher in cases with abnormal karyotype compared to patients with normal karyotype (p=0.021). Global analysis showed a positive correlation between CKS1B expression and 1q21 copy number (p<0.0001). No association between CKS1B mRNA expression and clinical parameters was found. However, a significantly higher level of β2 microglobulin in cases with 1q21 gains than those without (p=0.0094) was observed. Overall survival was shorter in cases with 1q21 gain compared to those with normal 1q21 region (p=0.0082). Our results suggest a role for CKS1B in the multiple step process of progression of MGUS to MM and show that CKS1B copy gain has a more significant prognostic value than its overexpression. This adverse impact on survival probably reflects the genetic instability associated to chromosome 1q alterations resulting in a more aggressive behavior of the disease.

Keywords: CKS1B gene expression; FISH; MGUS; Multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • CDC2-CDC28 Kinases / genetics*
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 1
  • Disease Progression
  • Female
  • Gene Dosage*
  • Gene Expression Profiling
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Monoclonal Gammopathy of Undetermined Significance / diagnosis
  • Monoclonal Gammopathy of Undetermined Significance / genetics*
  • Monoclonal Gammopathy of Undetermined Significance / mortality
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / mortality
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics*
  • Young Adult

Substances

  • CKS1B protein, human
  • RNA, Messenger
  • CDC2-CDC28 Kinases