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Review
. 2023 Mar 9;15(6):1684.
doi: 10.3390/cancers15061684.

Optical Genome Mapping for Cytogenetic Diagnostics in AML

Verena Nilius-Eliliwi  1 , Wanda M Gerding  2 , Roland Schroers  1 , Huu Phuc Nguyen  2 , Deepak B Vangala  1
Affiliations
Review

Optical Genome Mapping for Cytogenetic Diagnostics in AML

Verena Nilius-Eliliwi et al. Cancers (Basel). .

Abstract

The classification and risk stratification of acute myeloid leukemia (AML) is based on reliable genetic diagnostics. A broad and expanding variety of relevant aberrations are structural variants beyond single-nucleotide variants. Optical Genome Mapping is an unbiased, genome-wide, amplification-free method for the detection of structural variants. In this review, the current knowledge of Optical Genome Mapping (OGM) with regard to diagnostics in hematological malignancies in general, and AML in specific, is summarized. Furthermore, this review focuses on the ability of OGM to expand the use of cytogenetic diagnostics in AML and perhaps even replace older techniques such as chromosomal-banding analysis, fluorescence in situ hybridization, or copy number variation microarrays. Finally, OGM is compared to amplification-based techniques and a brief outlook for future directions is given.

Keywords: AML; Optical Genome Mapping; WGS; cytogenetics; whole-genome sequencing.

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Conflict of interest statement

V.N.-E.: Congress/Travel fees: Jazz Pharmaceuticals, Falk Foundation. DBV: Speaker’s honoraria: Pfizer, Abbvie, Falk, and Roche; Advisory Bords: Pfizer, Gilead, and Bristol Myers Squibb; Congress/Travel fees: Gilead, Abbvie, and Celgene. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
OGM workflow. After acquisition from blood or bone marrow, samples are either frozen or transferred to a lab. Ultra-high-molecular-weight (UMWH) DNA is prepared and labelled at CTTAAG sequence with a fluorochrome. The samples are transferred on a chip for linearization through nanochannels and run on a Bionano Saphyr® system for detection by fluorescence microscopy. The genome is aligned according to a reference genome and analyzed through various algorithms with analysis of structural variants (SV) and according to copy number changes. Depicted timeline on the right shows minimum number of days required to analyze one sample.
Figure 2
Figure 2
Schematic Graphical illustration of standard cytogenetic methods and OGM based on the data of Gerding et al. and Vangala et al. (quantitatively inaccurate) [27,28]. The vast majority of variants detected by conventional methods are visible by OGM, which, furthermore, enables the detection of a wider range of aberrations, i.e., novel variants, not visible by other techniques. However, a subset of variants, especially in highly repetitive regions such as telomeres and centromeres, might not be detected.
See this image and copyright information in PMC

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