b'sequences are present and in how many copies (Figure 2). TheGeneChip probe array Hybridized probe featureadvantage of microarrays is that hundreds of thousands to Single-stranded, uorescently millions of sequences can be interrogated in a single experiment.labeled DNA targetIf the appropriate probes that detect specific mutations areOligonucleotide probepresent on the chip, they can also detect common SNP variants.24 mBoth copy number aberrations (CNAs) and somatic mutationsEach probe feature contains millions of copies of a specic are important drivers of hematological malignancies. Cytogeneticoligonucleotide probeOver 200,000 dierent investigation of these malignancies has become an integral partprobes complementary of disease evaluation, prognosis, and prediction of response toto genetic information of interesttherapy. Current analysis of hematological malignancies involves multiple sequential tests and laborious workflows. However, implementation of high-resolution copy number microarrays inImage of hybridized probe arrayresearch laboratories has created an unprecedented opportunityAutomated MicroarrayData analysis or manual to profile multiple relevant driver events in hematologicalsample prep processing and reportingmalignancy samples. Whole-genome microarrays that cover both Sample typesblood orHigh throughputwhole- Data analysispolymorphic (e.g., single-nucleotide polymorphisms, or SNPs)bone marrow genome copy numberidentification of analysis on the Appliedamplifications or deletions, and nonpolymorphic regions of the genome can be used toSample input200 ngBiosystems GeneChipLOH, cnLOH, ploidy, and assess DNA copy number alterations at much higher resolutionDNA Scanner 3000 7G System breakpoint determinationSample preparation Automated reportingthan with conventional cytogenetic analyses. automated on theOncomine Knowledgebase NIMBUS TargetReporter for myeloid cancerPreparation Instrument, The Applied Biosystems CytoScan HD Suitecomprisingor manual preparationmicroarrays, reagents, and analysis softwareis aFigure 2. Basics of a microarray assay.comprehensive, high-resolution, whole-genome solutionFinally, the Applied Biosystems Axiom Precision Medicine designed to assist in the understanding and characterization ofResearch Array includes over 800,000 genotyping probes. biomarkers in hematological malignancies. The CytoScan HDThe targets on this array were selected to emphasize variants assay interrogates all relevant CNAs associated with lymphoidthat are commonly seen in clinical research, including common and myeloid disorders using a single microarray-based assay.cancer variants, clinically actionable variants, pharmacogenomic The assay covers all the major lymphoid disorders associatedvariants, and more. The common cancer markers were chosen with acute lymphocytic leukemia (ALL) and chronic lymphocyticfrom the list of published variants associated with cancer leukemia (CLL), as well as myeloid disorders associated withphenotypes identified via a genome-wide association study acute myeloid leukemia (AML), myelodysplastic syndrome(GWAS), as per the National Human Genome Research Institute (MDS), chronic myeloid leukemia (CML), and multiple myelomaand the European Bioinformatics Institute (NHGRI-EBI) GWAS (MM). In addition to superior performance, the CytoScan HDCatalog, as well as some recently published and unpublished Suite does not require additional cell culture or cell arrest priorcancer-associated SNPs. The clinically actionable variants to karyotyping. include relevant variants from ClinVar and enable assessment The Applied Biosystems OncoScan CNV Plus Assay is aof actionable genetic risk across a wide range of populations. microarray-based whole-genome copy number assay designedFinally, the pharmacogenomic variants in the array prioritize to query genomic DNA that has been degraded, such as DNAvariants that are derived from the Clinical Pharmacogenetics extracted from FFPE samples. It enables the detection of relevantImplementation Consortium (CPIC) guidelines and variants copy number variants (CNVs) such as copy number gain andcontributing to star alleles.loss, LOH, cnLOH, ploidy, allele-specific changes, mosaicism, clonal heterogeneity, and chromothripsis. It also includes probes that can query a panel of driver somatic SNPs commonly found in solid tumors. Similarly, the Applied Biosystems OncoScan CNV Assay has the same copy number coverage as the OncoScan CNV Plus Assay, but does not include somatic SNP mutation probes. Contents 15'