Whole Genome Array

One Platform for LOH and CNVs

Haematological cancers –¬†detection of copy number changes and loss of heterozygosity on a single array for the haematological malignancies Chronic Lymphocytic Leukaemia (CLL), Multiple Myeloma (MM), Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS).

The CytoSure Haematological Cancer +SNP array combines long oligo array comparative genomic hybridisation (aCGH) probes for superior copy number detection with fully research-validated single nucleotide polymorphism (SNP) content for accurate identification of loss of heterozygosity (LOH) without concurrent changes in gene copy number. The array content has been optimised to target regions known to be important in haematological cancers while providing good backbone coverage. The complimentary, industry-leading CytoSure Interpret Software allows intuitive, single-click data analysis (Figure 1).

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Figure 1: CytoSure Interpret Software enables easy and accurate detection of aberrations and breakpoints. A complex set of aberrations for a CLL sample on chromosome 17 are shown (yellow shading)*. Tracks shown below the aberrations enable verification of regions of interest. Aberrations identified in previously analysed samples are also clearly identified, shown as bright blue tracks.

Confident detection of CNV and LOH on a single array

aCGH is the gold standard for detecting copy number variation (CNV)1; however, until recently it was not possible to combine this technique with SNP analysis and LOH detection, meaning either 2 separate arrays were needed or inferior SNP-based CNV detection platforms1 were used.The CytoSure Haematological Cancer +SNP array combines aCGH-based CNV detection with fully research-validated SNP content, allowing confident and cost-effective CNV and LOH identification using a single array. Due to the unique design of the SNP probes, where an intensity-based comparison is made between the two SNP probes, there are no changes to the standard aCGH protocol, no restriction digest is required and any reference sample can be used (Figure 2). For optimum performance, the array can be combined with the CytoSure Genomic DNA Labelling Kit, which offers high signal intensities enabling easier allele discrimination.

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Figure 2: CytoSure Interpret Software calculates the percentage of homozygous and heterozygous SNPs for each chromosome. Chromosome 17 is shown from a CLL sample*. Below the chromosome image red lines indicate homozygous alleles, black heterozygous. Regions of LOH are indicated by a dark red solid rectangle and aberrations, if present, are shown above each chromosome – in this sample there is a deletion, indicated by a bright red rectangle. With 91% homozygous SNPs, on the p arm, chromosome 17 presents a clear example of a 17.64mb region of LOH. The size of the LOH region and the ‘score’ for that region is given in the table. The LOH region covers 43 genes.

Optimised design allows the identification of key genomic aberrations

Oxford Gene Technology (OGT) has worked in collaboration with leading researchers to develop the CytoSure Haematological Cancer +SNP array. This array provides standardised, evidence-based content, in addition to offering whole genome ‘backbone’ coverage. This enables confident detection of commonly occurring trisomies such as chromosome 12, while being able to detect complex rearrangements (Figure 1). CytoSure arrays utilise 60-mer oligonucleotide probes, which have been shown to offer higher signal-to-noise ratios and increased specificity and sensitivity1.

Cancer-specific tracks enabling fast and easy data generation and interpretation

CytoSure Interpret Software, which accompanies all CytoSure arrays, is a powerful, easy-to-use package for the analysis of CNV and SNP data. Innovative features such as the Accelerate Workflow enable the automation of data analysis workflows, minimising the need for user intervention and maximising the consistency and speed of data interpretation. Data storage and retrieval has been streamlined – the robust SQL database enables sophisticated data querying and filtering. CytoSure Interpret Software also includes extensive cancer-specific annotation tracks, including CLL regions from the Mitelman Database, the Cancer Gene Census Genes and the Haematology Regions from the Atlas of Genetics and Cytogenetics in Oncology and Haematology.

The data from Hurles et al (2010)2 is also available as an annotation track to aid identification of haploinsufficient genes using a predictive probability model generated by comparing key evolutionary and functional similarities between genes whose function is sensitive to a loss of a single copy. Each track links to online resources providing results in context.

Haematological Cancer + SNP Array – Ordering Information

020070 | CytoSure Haematological Cancer +SNP (8x60k) | CLL, MM, MPN and MDS

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