Cytogenetic Aberrations in Myelodysplastic Syndrome Detected by Comparative Genomic Hybridization and Fluorescence In Situ Hybridization

Abstract

Conventional cytogenetics (CC) is proven as a diagnostic and prognostic factor in myelodysplastic syndrome (MDS). However, CC may be hampered by insufficient metaphase preparation and cannot analyze interphase nuclei. These problems are solved by using comparative genomic hybridization (CGH). The CGH was applied to samples from 45 patients with MDS, and the results were compared with CC and fluorescence in situ hybridization (FISH). The CC detected aberrations in 12 of 45 samples, including chromosomes 3 (n = 1), 5 (n = 9), 7 (n = 2),8(n = 1), 18(n = 1),21 (n = 1), X (n = 1), and Y(n = 2). In one patient, loss of B and C group chromosomes and a marker chromosome were seen. The CGH revealed chromosomal imbalances in 18 of 45 samples, including chromosomes 5 (n = 11), 7 (n = 2), 8 (n = 1), 18(n = 1), 20(n = 1), 21 (n = 1), X (n = 1), and Y (n = 2). All unbalanced aberrations found by CC were detected by CGH, too. In two patients, the CGH found additional aberrations and redefined the aberrations of the chromosomes of the B and C group in one sample. The FISH confirmed these aberrations. Additionally performed FISH for chromosomes 5, 7, and 8 gave normal findings in all patients found to be normal in CC and CGH. The CGH and FISH confirmed the results obtained by CC. All three techniques showed changes of chromosomes 5 and 7 as the most frequent aberrations, emphasizing the importance of these chromosomes in the development of MDS. Furthermore, the CC is proven as the basic technique for cytogenetic evaluation of MDS.

High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival

“…Several groups have performed conventional and aCGH to identify genomic alteration in marrow cells from patients with MDS. [37][38][39][40][41][42][43] In general, these studies used total marrow cells as the source of DNA and did not focus on the low-risk MDS subtypes. Nevertheless, single nucleotide polymorphism (SNP) genotyping by 2 independent groups revealed some copy number alterations in accordance with our findings [43][44][45] (Table 2).…”

Whole genome scanning as a cytogenetic tool in hematologic malignancies

“…Early studies used BAC CGH for the investigation of genomic changes in various solid tumors and hematopoietic malignancies, including MDS. [49][50][51][52][53] CGH-A allowed for a wider application of this technology than very labor-intense chromosomal CGH. 54 The quality of CGH-A-based analysis is limited by the platform on which it is performed and depends on the density of BAC probes, varying from thousands to hundreds of thousands.…”

DNA profiling by arrayCGH in acute myeloid leukemia and myelodysplastic syndromes

“…Taking into account only published series that included more than ten patients studied with cCGH, nearly 120 MDS and 260 cases of AML have been reported (Bentz et al, 1995;El-Rifai et al, 1997;Huhta et al, 1999;Wilkens et al, 1999;Castuma et al, 2000;Heller et al, 2000;Kim et al, 2001;Lindvall et al, 2001;Dalley et al, 2002;Casas et al, 2004;Babicz et al, 2005;Karst et al, 2005;Martinez-Ramirez et al, 2005). Compared with data obtained with classic cytogenetic methods, cCGH analysis yielded a higher number of well defined structural changes.…”