Molecular definition of chromosome arm 5q deletion end points and detection of hidden aberrations in patients with myelodysplastic syndromes and isolated del(5q) using oligonucleotide array CGH.

Isolated deletions of the long arm of chromosome 5, del(5q), are observed in 10% of myelodysplastic syndromes (MDS) and are associated with a more favorable prognosis, although the clinical course varies considerably. If one or more additional chromosomal aberrations are present, this correlates with a significantly shorter overall survival. To assess the frequency of hidden abnormalities in cases with an isolated cytogenetic del(5q), we have performed a genome wide high resolution 44 K 60mer oligonucleotide array comparative genomic hybridization (aCGH) study using DNA from bone marrow cells of 12 MDS and one AML patient. In one case a single additional hidden 5.6 Mb deletion of 13q14 and in another case multiple larger aberrations involving many chromosomes were found. Fluorescence in situ hybridization demonstrated that aberrations present in 35% of the bone marrow cells can be detected by aCGH. Furthermore with oligonucleotide aCGH the deletion end points in 5q were mapped precisely, revealing a cluster of proximal breakpoints in band q14.3 (n = 8) and a distal cluster between bands q33.2 and q34 (n = 11). This study shows the high resolution of oligonucleotide CGH arrays for precisely mapping genomic alterations and for refinement of deletion end points. In addition, the high sensitivity of this method enables the study of whole bone marrow cells from MDS patients, a disease with a low blast count.