Chromosome 2 aberrations in clinical cases characterised by high resolution multicolour banding and region specific FISH probes

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Abstract
The field of human cytogenetics has been through many different stages of development, each of them improving the characterisation of structurally abnormal and/or supernumerary chromosomes. The era of reliable identification of human chromosomes started with the invention of the banding method by Dr Lore Zech in 1968.1 The introduction of fluorescence in situ hybridisation (FISH) techniques in human cytogenetics by Pinkel et al 2 in 1986 allowed specific staining of chromosomes and chromosomal subregions. Even though G banding3 is still the gold standard against which all molecular cytogenetic techniques are measured, this technique based on alternating light and dark bands can lead to equivocal chromosome breakpoints.4 The development of multicolour FISH5 in 1996, multiplex FISH (M-FISH),6 and spectral karyotyping (SKY),7 allowing the simultaneous and specific painting of all 24 human chromosomes in different colours, was helpful in overcoming these problems in part. However, they are not suited for the detection of inversions or duplications or for more precise determination of chromosome breakpoints. Several FISH based techniques that are capable of solving this problem have been developed in the last decade: the application of chromosome arm specific probes,6,8 the use of chromosome bar codes,9,10 the cross species colour banding (RX-FISH) approach,11 and the high resolution multicolour banding technique (MCB).12,13 The latter approach can cover the entire karyotype with human DNA probes without leaving any gaps. To illustrate the power of the MCB technique, clinical cases with five different kinds of aberrations identified by conventional banding techniques, that is, translocations (four cases), deletions (two cases), duplications (three cases), inversions (two cases), and small supernumerary marker chromosomes (one case), were reinvestigated. In 9/11 cases (∼80%), the chromosome breakpoints were redefined by MCB and these results have been confirmed by locus …