Bella Liu is a third year Pathology Resident of Icahn School of Medicine of Mount Sinai who is interested in gastrointestinal pathology and molecular pathology. She has spent most of her time focusing on diagnostic skills but also has contributed to various research projects, involved in multiple molecular studies. Bella Liu is a trainee member of Cancer Genomics Consortium, United States and Canadian Academy of Pathology, as well as College of American Pathologists. In her spare time, Bella loves to watch horror movies, play mobile games and go hiking.
Bella Liua, William Lamb
aIcahn School of Medicine at Mount Sinai, New York, NY, USA; bMount Sinai Hospital, New York, NY, USA
In multiple myeloma and monoclonal gammopathies, single nucleotide variants (SNV), copy number variants (CNV) and IGH-rearrangements with prognostic/therapeutic relevance, are assessed by NGS, FISH, and karyotype. Recently, whole exome/transcriptome sequencing (WES/WTS) post CD138+-enrichment has been clinically implemented, thus we evaluated this approach to detect relevant alterations. Over 9 months, 160 aspirates were enriched including assessment of %CD138+ by flow cytometry post-enrichment. Extracted DNA/RNA were sent out for WES/WTS (20% tumor cellularity cut-off). Eighteen were insufficient where DNA yield correlated with WES/WTS success by Welch Two Sample t-test (p<0.001). Of 142 reported, post-enrichment %CD138 correlated with the detection of relevant SNV or CNV (n=97) (p<0.001), and after excluding those only displaying CHIP-associated SNVs (n=11) (p<0.00001). FISH was performed outside on similarly enriched CD138+ cells (collected during same procedure) for 122 cases. While the specificity was ?91%, the sensitivities of detection by WES of gain of 1q, 9, 11, 15 and loss of 1p, 13/13q14, 17p/17, were 70%, 79%, 76%, 79%, and 71%, 67%, 83% respectively. Lack of detection was primarily in cases with FISH-detected gain/loss <20%. For 10 cases with IGH-FGFR3 and 6 with IGH-MAF (by FISH), 9 had detectable IGH-NSD2 and 3 IGH-WWOX fusion transcripts respectively. Thus, WES/WTS is less sensitive than FISH for detection of CNV <20%, but affords the detection of additional relevant abnormalities (4p, 16q loss). Increasing the dataset will afford the establishment of cut-offs for DNA yield and %CD138+ to improve overall diagnostic yield, and for the level of CCND1 transcripts that correlate with IGH-CCND1 rearrangement.