Genome-wide arrays in routine diagnostics of hematological malignancies

Abstract

Over the last three decades, cytogenetic analysis of malignancies has become an integral part of disease evaluation and prediction of prognosis or responsiveness to therapy. In most diagnostic laboratories, conventional karyotyping, in conjunction with targeted fluorescence in situ hybridization analysis, is routinely performed to detect recurrent aberrations with prognostic implications. However, the genetic complexity of cancer cells requires a sensitive genome-wide analysis, enabling the detection of small genomic changes in a mixed cell population, as well as of regions of homozygosity. The advent of comprehensive high-resolution genomic tools, such as molecular karyotyping using comparative genomic hybridization or single-nucleotide polymorphism microarrays, has overcome many of the limitations of traditional cytogenetic techniques and has been used to study complex genomic lesions in, for example, leukemia. The clinical impact of the genomic copy-number and copy-neutral alterations identified by microarray technologies is growing rapidly and genome-wide array analysis is evolving into a diagnostic tool, to better identify high-risk patients and predict patients' outcomes from their genomic profiles. Here, we review the added clinical value of an array-based genomewide screen in leukemia, and discuss the technical challenges and an interpretation workflow in applying arrays in the acquired cytogenetic diagnostic setting.

Genomic profiling of myeloma: the best approach, a comparison of cytogenetics, FISH and array-CGH of 112 myeloma cases

“…(Biodiscovery, El Segundo, California, USA). Copy number variant (CNV) calls were visually reviewed and interpreted as described by Simons 17. Where necessary, the diploid (2N) value was adjusted, based on FISH results.…”

Somatic mutations found in the healthy blood compartment of a 115-yr-old woman demonstrate oligoclonal hematopoiesis

“…Moreover, no gross chromosomal abnormalities characteristic of leukemia were detected in W115's WBCs by CGH array analysis or in the sequencing data (Supplemental Fig. S8), thereby excluding the presence of CML, most forms of precursor B-ALL, and AML (Simons et al 2012). …”

Use of Single Nucleotide Polymorphism Array Technology to Improve the Identification of Chromosomal Lesions in Leukemia

“…This approach was initially used for research purposes to discover novel disease-related aberrations. Several efforts have been made to standardize analysis for clinical and diagnostic purpose [7, 30]. However, SNP array remains limited in the detection of balanced rearrangements and inversions without DNA losses; therefore, FISH is still useful to interpret complex rearrangements or to distinguish tandem from dispersed duplications.…”

“…Although these techniques enable the detection of only unbalanced defects and do not distinguish between multiple large clones, they have greater resolution compared with classical cytogenetic methods. Moreover, SNP array has the advantage of simultaneous genotyping, enabling detection of copy number neutral loss of heterozygosity (CN-LOH), also referred to as somatic uniparental disomy (UPD) [5-7]. This review emphasizes the newest findings obtained from genome-wide analysis of genetic aberrations in chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML).…”