35 - Chromosomal Microarray in the Era of Next Generation Sequencing: Still Going Strong and Making a Difference in Patient Care. Cases from Medical University of South Carolina

Abstract

Whole genome chromosomal microarray analysis provides excellent copy-number variation (CNV) and loss of heterozygosity (LOH) data with high sensitivity, specificity and reproducibility. However, since next-generation sequencing (NGS) technologies appeared on the market, remarkable progress has been made in terms of speed, read length, and throughput. These advances, as well as a significant decrease in the cost, have facilitated integration of NGS applications into clinical diagnostics. The ability to detect CNV and LOH from NGS data would extend the utility of this powerful approach that has mainly been used for detection of point mutations or small insertion/deletions. Consequently, clinical laboratories are considering NGS as a sole platform for studies of all the types of genetic aberrations. However, currently chromosomal microarray is the best option for discerning CNV and LOH events both technically (in terms of whole genome coverage, breakpoint resolution, sensitivity, specificity, robust results) and financially. We present several cases that illustrate the utility of chromosomal microarray assessment for (i) diagnosis: child born with massive constitutional UPD, reclassified cases of biphenotypic leukemia and renal cell carcinoma, (ii) prognosis— case of pediatric ALL with small deletions of important prognostic genes, adult high grade MDS transforming to AML with HER2 amplification, and (iii) treatment—a Ph-like B-ALL with rare gene fusion and adolescent pre B-ALL with atypical deletion of mismatch repair gene. In conclusion, an integrated approach combining analysis of CNVs and LOH by microarray with NGS interrogation of clinically important SNPs and small insertions/deletions is the best alternative for comprehensive genomic diagnostics.