Application of array-based whole genome scanning technologies as a cytogenetic tool in haematological malignancies

Summary

Karyotypic analysis provides useful diagnostic information in many haematological malignancies. However, standard metaphase cytogenetics has technical limitations that result in the underestimation of the degree of chromosomal changes. Array-based technologies can be used for karyotyping and can supplant some of the shortcomings of metaphase cytogenetics, and include single nucleotide polymorphism arrays (SNP-A) and comparative genomic hybridization arrays (CGH-A). Array-based cytogenetic tools do not rely on cell division, have superb resolution for unbalanced lesions and allow for the detection of copy number-neutral loss of heterozygosity, a type of lesion not seen with metaphase cytogenetics. Moreover, genomic array analysis is automated and results can be objectively and systematically analysed using biostatistical algorithms. As a potential advantage over genomic approaches, metaphase cytogenetics can detect balanced chromosomal defects and resolves clonal mosaicism. Initial studies performed in various haematological malignancies indicate the potential of SNP-A-based karyotyping as a useful clinical cytogenetic detection tool. The current effort is aimed at developing rational diagnostic algorithms for the detection of somatic defects and the establishment of clinical correlations for novel SNP-A-detected chromosomal defects, including acquired somatic uniparental disomy. SNP-A can complement metaphase karyotyping and will probably play an important role in clinical cytogenetic diagnostics.