58P Molecular Investigation Using Microarray-Based Comparative Genomic Hybridization in Patients with Myelodysplastic Syndrome and Normal Karyotype

Myelodysplastic syndromes (MDS) are a group of blood cancers which are characterized by ineffective hematopoiesis of bone marrow cells and abnormal blood cell development leading to cytopenias and an increased risk for progression to acute myeloid leukemia. At diagnosis, 50% of MDS patients have a normal conventional karyotype, however, unbalanced chromosomal aberrations are common and have prognostic implications. We aimed to investigate the unbalanced chromosomal aberrations in MDS patients with normal bone marrow karyotype using micro-array-based Comparative Genomic Hybridization (aCGH). aCGH was performed on peripheral blood extracted DNA from 5 patients with clinical MDS features and normal bone marrow karyotype and we employed a Multiplex Ligation-dependent Probe Amplification (MLPA®) analysis to confirm the Subtelomeric copy number variations (CNVs). The aCGH analysis (NCBI36/hg18) revealed copy-number variations (CNV) in all patients with normal karyotype. All the 5 patients carried 16 copy-number variations (CNV), including 8 duplications ranging from 20 killobases (Kb) to 2,283 megabases (Mb), they include chromosomal regions 1q44; 2p16; 5q12, 10q27;14q12; 22q11; Xq21.3; Xq27.3 and 8 deletions ranging from 26.3 Kb to 948.9 kb, including chromosomal regions 1p36.1; 1q21; 4q31; 5p15.4; 9q21.1; 10q24; 22q21. Subtelomeric CNV (5p15; 10q27 and 1q44) were approved by using Multiplex Ligation-dependent Probe Amplification (MLPA®) analysis with SALSA MLPA Probemix P036 Subtelomeres Mix 1. These results demonstrated that chromosomal defects in MDS may be more frequent than predicted by metaphase cytogenetics and new cryptic lesions may be revealed by precise analysis methods. This study suggests a significant role for the use of aCGH in the clinical workup of MDS patients.