53. Clinical whole exome/whole transcriptome (WES/WTS) analysis detects copy number and structural rearrangements important

Abstract

<h3>Background</h3> Chromosomal copy number alterations (CNAs) and structural rearrangements (SR) are a key part of risk stratification and management of patients with MM. We developed a clinical paired tumor/normal WES/WTS assay that detects CNAs at one-copy difference from focal to whole genome, and gene fusion at 20% and 10% limit of detection, respectively. <h3>Patients and Methods</h3> We performed WES/WTS analysis utilizing DNA/RNA extracted from CD138+ enriched cells and buccal swab from 92 MM patients. Plasma cell content was not available for most cases. We compared the detection of CNAs, and SR with other techniques currently in use including FISH, arrays and molecular analysis. <h3>Results</h3> Molecular alterations (MA) were present in 82/92(89.1%) cases, whereas 65/92(69.5%) cases had CNAs. In cases with CNAs (indicating sufficient tumor content), deletions of (1p32), (1p12), or both were detected in 7(10.8%), 12(18.5%), and 5(7.7%) cases, respectively. Gain of (1q22), and hyperdiploidy were detected in 19(29.2%) and 32(49.2%), respectively. Deletions of 13q, 14q, 16q, and 17p(TP53) were detected in 32(49.2%), 14(21.6%), 16(24.6%), and 13(20%) cases, respectively. In cases with MA, 10/82(10.8%), and 3(3.6%) cases had TP53 mono and bi-allelic inactivation, respectively. Translocations (4;14)(p16;q32)(IGH::NSD2/FGFR3) and t(14;16)(q32;q23)(IGH::MAF) were detected in 11(11.9%), and 3(3.7%) cases with MA, respectively. Overexpression of CCND1 (research use only) was observed in 8/82(9.7%) cases. <h3>Discussion</h3> Our WES/WTS detected abnormalities in this series similarly to what has been reported by techniques currently needed in combination such as FISH, arrays or molecular analysis. By incorporating RNA expression analysis, WES/WTS may reliably detect all clinically-relevant alterations in MM.