Project Details
Projekt
Core facility for molecular cytogenetics, genetic diagnostics and profiling
Applicants
Professor Dr. Lars Bullinger; Dr. Christian Langer
Subject Area
Hematology, Oncology
Term
from 2009 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 100308792
During the last funding period we have established a centralized sample collection within the Clinical Research Unit (CRU). Patient samples from the University of Würzburg as well as from the University of Ulm have been characterized for cytogenetic and molecular genetic changes. The CD138 purified plasma cells are processed for archiving of tumor sample slides and of tumor cell pellets for further analysis. Additionally, corresponding germline material is archived as reference control. High-resolution genome-wide screening for genetic alterations of MM samples was performed using SNP chip analysis (Affymetrix Microarray Human Genome SNP 6.0). During the next funding period we will expand the collection of clinical samples. The incorporation of well characterized patients from clinical trials run by the German Study Group on Multiple Myeloma (DSMM) will strengthen the tumor bank and will serve as an invaluable resource for translational research within the CRU. The recently published characterization of the mutational landscape of 38 MM tumor genomes through massively parallel sequencing highlighted new aspects of the pathogenesis of multiple myeloma including the detection of novel mutated candidate genes.Consequently, we will put a special focus on a refined molecular characterization of the primary MM samples by the use of novel next-generation sequencing (NGS) technologies. From a number of MM samples from very well characterized patients participating in DSMM trials we will perform a mutational screen in a comprehensive set of target genes: NRAS, KRAS, BRAF, TP53, DIS3, FAM46C, KDM6A [also known as UTX], TRAF3, CYLD, CDKN2A/CDKN2B and CDKN2C. This research will be accompanied by a transcriptome sequencing (RNA-seq) approach in order to allow integrative analyses of DNA variation and gene expression changes. Furthermore, RNA-seq data offers the possibility to detect MMassociated fusion genes as well as aberrant/differential splicing patterns which recently have been shown to be also of pathogenetic relevance. Similarly, over the last decade small noncoding RNAs, particularly microRNAs (miRNA) were identified as key regulators of normal and pathological hematopoiesis. However, the role of miRNAs in the development of plasma cell disorders and the oncogenic pathways that lead to the development of MM is not fully understood. Therefore, we will also try to identify differential expression patterns of miRNAs in various MM subgroups investigated by the CRU projects.
DFG Programme
Clinical Research Units
