An analysis of complex chromosomal aberrations in seven cases of myelodysplastic syndromes by M-FISH and whole chromosome painting.

Complex chromosomal aberrations (CCAs) can be detected in a substantial proportion of myelodysplastic syndrome (MDS). Comprehensive analysis of the chromosomal rearrangements in these CCAs has been hampered by the limitations of conventional cytogenetics (CC). Multiplex fluorescence in situ hybridization (M-FISH) is a new generation FISH technique which allows simultaneous identification of all the 24 human chromosomes. So it is very useful in clarifying CCAs, identifying cryptic interchromosomal rearrangements and characterizing marker chromosomes. But it also has some limitations. We used M-FISH and whole chromosome painting (WCP) to accurately refine the CCAs revealed by R-banding CC in seven cases with MDS. The composition and origin of 6 kinds of marker chromosomes, nine kinds of chromosomes with additional material undetermined and five kinds of derivative chromosomes undefined by CC were defined after M-FISH analysis. Four kinds of cryptic translocations overlooked by CC were found on derivative chromosomes and previously normal appearing chromosomes. In addition, M-FISH revealed some nonrandom aberrations which most frequently involved chromosome 17 (5/7) and -5/5q-(4/7). Fluorescence flaring is a main factor leading to misinterpretations. Some misclassified and missed chromosomal aberrations by M-FISH were corrected by WCP. M-FISH is a powerful molecular cytogenetic tool in clarification of CCAs. Complementary WCP can further identify misclassified and missed chromosomal aberrations by M-FISH. CC in combination with molecular cytogenetic techniques including M-FISH and WCP can more precisely unravel CCAs.