P-341: Use of Optical Genome Mapping in the Cytogenetic Diagnosis of Multiple Myeloma

Introduction: Prognosis of patients with multiple myeloma (MM) is highly heterogeneous. Most of them present genetic alterations and chromosomal abnormalities, with translocations persisting throughout the disease. Cytogenetic studies are usually performed using specific fluorescence in situ hybridization (FISH) probes on selected CD138+ plasma cells. Recently, a new diagnostic technique based on the optical mapping of the genome (Optical Genome Mapping, OGM) is available, which allows the detection of both structural alterations and copy number changes at the whole genome level in a single assay. The main objective of this work was to evaluate and compare OGM performance in total bone marrow (BM) with FISH conducted in selected plasma cells.

Methods: A total of 10 patients diagnosed with MM were included in this study. All cases were analyzed by FISH on selected CD138+ plasma cells. In parallel, high molecular weight DNA was extracted from total BM, fluorescently marked with the DLE-1 enzyme, and charged in a Shapyr chip for analysis in a Shapyr system (Bionano, San Diego, CA, USA).

Results: The median age of the patients was 56.5 years old (range, 31–83). Seven were R-ISS stage II and three R-ISS III. Median BM infiltration by plasma cells was 22.5% (range, 6–85%). FISH detected alterations in 8 patients, was negative in 1 patient and non-assessable in 1 case. All patients included in the study were assessable by OGM.
In patients #1 and #10, FISH and OGM were concordant, but OGM detected more chromosomal alterations, including multiple losses and gains of material, translocations, and monosomies. Regarding patient #2, with a negative FISH panel, OGM detected multiple CNV and a t(8;18) resulting in a potential TCF4::MYC fusion gene. OGM resolved the case with non-assessable FISH (patient #3) and detected multiple CNV, including a deletion of TP53. Patients #4, #5, #8, and #9 with positive FISH results had a negative result by OGM, likely in the context of low infiltration of plasma cells in BM. Likewise, cases #6 and #7 had a non-concordant result between FISH and OGM, given that OGM did not detect the alterations found by FISH.

Conclusions: In this study, we analyzed the potential use of OGM in cytogenetic diagnosis of MM using total BM. Our preliminary data suggest that OGM is useful to detect chromosomal alterations and CNV in cases with negative and non-assessable FISH, particularly in patients with high BM infiltration of plasma cells. However, we observed that OGM was negative and non-concordant with FISH for some patients with low plasma cell infiltration and further, refining CD138+ selection will be needed to extend OGM to patients with low BM infiltration.