Conventional and molecular cytogenetic techniques and their application in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow diseases characterized by peripheral cytopenias due to ineffective hematopoiesis and susceptibility to leukemic transformation. The evolution of the disease proceeds in accordance with the multi-step theory of carcinogenesis and can thus serve as an important model in furthering our understanding of the processes involved in cancer transformation. Using metaphase cytogenetics, it is possible to detect abnormalities consisting of partial or complete chromosome deletions or additions, whereas translocations are rare, in approximately 50% of cases. Molecular cytogenetics, including fuorescence in situ hybridization (FISH), spectral karyotyping (SKY), and comparative genomic hybridization (CGH) can give additional information useful to identify risk-adapted approach to MDS patients. This chapter will review in details the new technology of SNP arrays recently applied in the field, to detect gains, losses and copy neutral-loss of heterozigosity (CN-LOH) or uniparental disomy (UPD). Since chromosomal alterations cause overexpression of oncogenes or inactivation of tumor suppressor genes, the precise molecular description of unusual aberrations may provide useful hints for better understanding the pathogenesis of this disease, identification of genes involved in the progression of MDS to leukemia, and tailoring patient management. Finally, we report a serial application of high resolution genomic array analysis at different stages of the disease allowing description of cryptic abnormalitie such as copy-neutral loss of heterozygosity (CN-LOH) not detected by conventional cytogenetics, to guide the search for point mutations in genes located in these regions and to define the temporal order of acquisition of other genetic abnormalities in MDS. © 2013 by Nova Science Publishers, Inc. All rights reserved.