Project Details
Projekt
Identification of relevant genes in the pathogenesis of multiple myeloma using whole genome DNA methylation analyses
Applicant
Dr. Martin Kaiser
Subject Area
Hematology, Oncology
Term
from 2010 to 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 190827152
Multiple myeloma (MM) is a malignant clonal disease of the bone marrow originating from terminally differentiated B-lymphocytes, so-called plasma cells. Generally, the disease is preceded by a pre-malignant stage, termed monoclonal gammopathy of undetermined significance (MGUS). In the clinical course of MM, a more aggressive type of cancer, called plasma cell leukaemia (PCL), can evolve. The pathomechanisms underlying the progression from MGUS to MM and PCL are to date unknown. Characteristic for MM is the stepwise accumulation of genetic lesions in the course of the disease.Recent evidence has shown that epigenetic alterations like DNA methylation may play an important role in the tumor biology of MM and that methylation patterns may change during progression.This project aims to perform whole genome DNA methylation analyses of approximately 120 bone marrow samples from myeloma patients using a bead array methylation assay. This high-resolution technique allows the parallel interrogation of the methylation status of about 27,000 so-called CpG dinucleotides throughout the genome.The detected MM methylation patterns are to be compared with the methylation status of healthy plasma cells, as well as with those of MGUS and PCL patients. Thus, differentially methylated genes or regions important for development and progression of the disease shall be identified. Genes of interest for tumor biology will be characterized by focused methylation assays and their functional role will be analyzed. Genes identified by these studies could serve as novel prognostic indicators or become targets for epigenetic therapies.
DFG Programme
Research Fellowships
International Connection
United Kingdom
