Whole genome SNP arrays for best practice for detection of diagnostic, prognostic and therapy related copy number changes and copy neutral-loss of heterozygosity across solid tumors and hematologic malignancies.

Abstract

e15575 Background: High resolution single nucleotide polymorphism (SNP) chromosomal microarrays (CMA) detect copy number changes and copy neutral-loss of heterozygosity (CN-LOH) across the entire genome, currently providing the best assessment for these types of genomic variants. Chromosomal microarrays are first tier tests utilized in the postnatal detection of microdeletions, microduplications and uniparental disomy/regions of homozygosity in constitutional disorders involving congenital abnormalities, developmental delay and intellectual disability. Methods: In the oncology setting, aberrations detected may be diagnostic, prognostic, and therapeutic. Because CMA assesses the entire genome and can readily detect aberrations as small as a single exon to as large as a whole chromosome, this is an important clinical tool to bridge the gap between low resolution of metaphase chromosome analysis and PCR-based short read sequencing-based assays. Results: No single genomic technique (metaphase chromosome analysis, FISH, CMA or Next Generation Sequencing, including large targeted gene panels) has the ability to detect all relevant information. Therefore, CMA should be considered an important clinical tool for solid and liquid tumors. Across a wide variety of solid tumors, whole genome assessment (including oncogene amplification, tumor suppressor loss, and copy number burden) leads not only to possible therapy targets but also to opportunities for participation in active clinical trials. Recently, the Cancer Genomics Consortium has published evidenced-based reviews on the clinical utility of CMA for copy number and CN-LOH assessment in a variety of hematologic malignancies, and similar papers in solid tumors are in review. Recognizing the growing evidence for CMA, the American Medical Association (AMA) CPT editorial board recently created a new Tier 1 test for cytogenomic arrays in neoplasia, and Centers for Medicare and Medicaid Services (CMS) approved crosswalking the price of the new code to the well-established constitutional cytogenomic array CPT code. Conclusions: For this presentation, examples of diagnostic, prognostic, and therapeutic utility and inclusion in clinical trials across many hematologic and solid tumor neoplasms will be presented to demonstrate the efficacy, cost effectiveness and sensitivity of whole genome assessment of copy number and copy neutral loss of heterozygosity