PhD Scientific Days 2023

Pathology - Posters D

Optical Genome Mapping in Acute Leukaemias: First Hungarian Experience with the Digital Cytogenomics

Text of the abstract

Introduction: Besides the modern molecular methods, detection of structural variants (SV) and copy number variations (CNV) using chromosome banding analysis (CBA) and Fluorescence In Situ Hybridization (FISH) still plays a major role in the diagnosis of haematological malignancies. Optical Genome Mapping (OGM) is a next-generation cytogenomic method that can simultaneously identify CNVs and SVs greater than 500 bp within 5 days without the need of cell cultures.

Aim: We aimed to detect chromosomal aberrations in acute leukaemias using OGM, and to test the feasibility of OGM in routine diagnostics in comparison with CBA and FISH analyses.

Methods: Ultra-high molecular weight DNA was isolated from 35 diagnostic or relapsed acute myeloid leukaemia (AML) and 2 blast phase chronic myeloid leukaemia samples. After labelling the DNA, data were collected by the optical system of the Saphyr instrument (Bionano, San Diego, USA) and were analysed using the Bionano Access software: SVs were described after standard and AML specific filtering, CNVs >5000kb without further filtering. Findings obtained by OGM were compared with CBA/FISH results of the same samples.

Results: A total of 70 CNVs were detected in 37 samples using OGM; 643 SVs with the standard and 84 SVs with the AML-specific filters. CBA and/or FISH was performed in 29 cases, among them 13 AML patients were classified into prognostic groups according to the 2022 ELN risk classification, while with OGM, 19 patients were classified. Complex karyotype (CK) was identified in 5 cases by CBA/FISH, and in 15 cases by OGM. In two cases, these results changed the intermediate prognostic classification defined by CBA/FISH to unfavourable. In the 29 samples (5 CK and 24 non-CK) where CBA/FISH were performed OGM showed full concordance with their results in 86%, in the CK and non-CK cases the concordance was 60 % and 92%, respectively. In addition, we detected 3 cases of KMT2A partial tandem duplication (intermediate prognosis) and 3 cases with MECOM gene rearrangements (poor prognosis).

Conclusion: The use of OGM allows the detection of clinically relevant aberrations in addition to those identified by conventional techniques, and therefore it seems to be a promising test for routine cytogenomic diagnostics.

Funding: FK20_134253 BO/00125/22 ÚNKP-22-5-SE-7 TKP2021-EGA-24 TKP2021-NVA-15 Richter Gedeon Talentum Foundation