Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma

E Jost; D Gezer; S Wilop; H Suzuki; J G Herman; R Osieka; O Galm

doi:10.1016/j.canlet.2009.02.002

Epigenetic dysregulation of secreted Frizzled-related proteins in multiple myeloma

Cancer Lett. 2009 Aug 18;281(1):24-31. doi: 10.1016/j.canlet.2009.02.002. Epub 2009 Mar 18.

Authors

E Jost¹, D Gezer, S Wilop, H Suzuki, J G Herman, R Osieka, O Galm

Affiliation

¹ Medizinische Klinik IV, Universitaetsklinikum Aachen, RWTH Aachen, Germany. ejost@ukaachen.de

PMID: 19299079
DOI: 10.1016/j.canlet.2009.02.002

Abstract

We analysed the clinical impact of epigenetic dysregulation of the Wnt pathway in malignant plasma cell disorders. In multiple myeloma (MM) cell lines, aberrant promoter hypermethylation of the secreted Frizzled-related protein (SFRP) genes was a common event, and hypermethylation of SFRP1,-2 and -5 was associated with transcriptional silencing. Among 76 primary patient samples, the frequency of aberrant methylation was 35.5% for SFRP1, 52.6% for SFRP2, 1.3% for SFRP4 and 6.9% for SFRP5. Hypermethylation of SFRP1 and -2 genes was detected in monoclonal gammopathy of undetermined significance and all MM stages including plasma cell leukaemia (PCL), while SFRP5 methylation was restricted to advanced MM stages and PCL. Our data indicate that epigenetic silencing of Wnt antagonists is an early event in MM pathogenesis and that SFRP5 hypermethylation may play a role in disease progression.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
Adult
Aged
Aged, 80 and over
Cell Line, Tumor / drug effects
Cell Line, Tumor / metabolism
CpG Islands*
DNA Methylation*
DNA, Neoplasm / metabolism*
Epigenesis, Genetic*
Eye Proteins / genetics*
Female
Humans
Infant, Newborn
Intercellular Signaling Peptides and Proteins / genetics*
Leukemia, Plasma Cell / genetics*
Leukemia, Plasma Cell / mortality
Leukemia, Plasma Cell / pathology
Male
Membrane Proteins / genetics*
Middle Aged
Multiple Myeloma / genetics*
Multiple Myeloma / mortality
Multiple Myeloma / pathology
Neoplasm Proteins / genetics*
Promoter Regions, Genetic / genetics
Proto-Oncogene Proteins / genetics*
Reverse Transcriptase Polymerase Chain Reaction
Sulfites / pharmacology
Survival Analysis
Wnt Proteins / physiology

Substances

Adaptor Proteins, Signal Transducing
DNA, Neoplasm
Eye Proteins
Intercellular Signaling Peptides and Proteins
Membrane Proteins
Neoplasm Proteins
Proto-Oncogene Proteins
SFRP1 protein, human
SFRP2 protein, human
SFRP4 protein, human
SFRP5 protein, human
Sulfites
Wnt Proteins
sodium bisulfite