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Optical Genome Mapping in Hematological Malignancies
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Optical Genome Mapping in Hematological Malignancies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 34931

Special Issue Editors

Dr. Adam C. Smith

E-Mail Website
Guest Editor
Cancer Cytogenetics Laboratory, Laboratory Medicine Program, University Health Network and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 2C4, Canada
Interests: genetics genomics & proteomics; cancer
Dr. Alex Hoischen

E-Mail Website
Guest Editor
Department of Human Genetics & Department of Internal Medicine, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherland
Interests: genomic technologies; immuno-genomics
Dr. Gordana Raca

E-Mail Website
Guest Editor
Director of Clinical Cytogenomics, Center for Personalized Medicine, Department of Pathology and Lab Medicine, Children's Hospital Los Angeles, Los Angeles, CA 90057, USA
Interests: cancer; tumor biology; pathology and biomarkers epilepsy; neurology genetics; environmental factors hematology; blood and marrow transplantation

Special Issue Information

Dear Colleagues,

For more than 40 years, the clinical evaluation of structural variation in hematological malignancies has primarily been driven by karyotyping.  Karyotyping is a robust tool for evaluating structural and numerical changes in leukemia and other malignancies due to its ability to visualize and catalogue recurrent changes to chromosomes.  As a result, many types of leukemia and lymphoma have a cytogenetic (i.e., karyotyping-based) classification system for diagnosis and prognosis.  However, karyotyping suffers from several challenges, including the need for dividing cells (metaphases) and the relatively “low resolution” of the technique.  Thus, ancillary testing, such as FISH or RT-PCR, is required to identify specific rearrangements between genes.  Optical Genome Mapping is a new technology that can detect structural variation within a sample at a much higher resolution than karyotyping.  As such, it is a promising new technique for the clinical evaluation of chromosomal changes in hematologic malignancies.  

The aim of this Special Issue is stimulate discussion around the use and adoption of Optical Genome Mapping for clinical diagnostics in hematological malignancies. 

  • Carry out the evaluation of optical genome mapping in different types of hematologic malignancies compared to conventional approaches or other novel technologies for structural and molecular classification;
  • Introduce interpretative systems, software tools, or other bioinformatics approaches to improve data analysis and reporting in hematologic malignancies;
  • Provide technical improvements or processes in hematologic malignancies that compare pre-analytical or analytical components in optical genome mapping to improve analysis, diagnostic sensitivity, etc.;
  • Produce novel research findings that may lead to novel diagnostic insights in the future.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  • Myeloid neoplasms;
  • Lymphoid neoplasms;
  • Plasma cell disorders;
  • Technical papers;
  • Economic utility analysis of OGM vs. other technologies;
  • Clinical research discoveries.

We look forward to receiving your contributions.

Dr. Adam C. Smith
Dr. Alex Hoischen
Dr. Gordana Raca
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Optical genome mapping
  • Myeloid neoplasia
  • Lymphoid neoplasia
  • Cytogenetics
  • Structural Variation

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Published Papers (10 papers)

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Editorial

Jump to: Research

6 pages, 1232 KiB  
Editorial
Cytogenetics Is a Science, Not a Technique! Why Optical Genome Mapping Is So Important to Clinical Genetic Laboratories
by Adam C. Smith, Alexander Hoischen and Gordana Raca
Cancers 2023, 15(22), 5470; https://doi.org/10.3390/cancers15225470 - 19 Nov 2023
Cited by 1 | Viewed by 2330
Abstract
Karyotyping is a technique that has been used in clinical cytogenetic laboratories for more than 40 years [...] Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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Research

Jump to: Editorial

19 pages, 2937 KiB  
Article
Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia
by Andrew Seto, Gregory Downs, Olivia King, Shabnam Salehi-Rad, Ana Baptista, Kayu Chin, Sylvie Grenier, Bevoline Nwachukwu, Anne Tierens, Mark D. Minden, Adam C. Smith and José-Mario Capo-Chichi
Cancers 2024, 16(9), 1693; https://doi.org/10.3390/cancers16091693 - 26 Apr 2024
Cited by 1 | Viewed by 1901
Abstract
Background: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A [...] Read more.
Background: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A partial tandem duplication (KMT2A-PTD), are particularly challenging to detect using standard molecular and cytogenetic approaches. Methods: We have validated the use of a custom hybrid-capture-based next-generation sequencing (NGS) panel for comprehensive profiling of AML patients seen at our institution. This NGS panel targets the entire consensus coding DNA sequence of KMT2A. To deduce the presence of a KMT2A-PTD, we used the relative ratio of KMT2A exons coverage. We sought to corroborate the KMT2A-PTD NGS results using (1) multiplex-ligation probe amplification (MLPA) and (2) optical genome mapping (OGM). Results: We analyzed 932 AML cases and identified 41 individuals harboring a KMT2A-PTD. MLPA, NGS, and OGM confirmed the presence of a KMT2A-PTD in 22 of the cases analyzed where orthogonal testing was possible. The two false-positive KMT2A-PTD calls by NGS could be explained by the presence of cryptic structural variants impacting KMT2A and interfering with KMT2A-PTD analysis. OGM revealed the nature of these previously undetected gene rearrangements in KMT2A, while MLPA yielded inconclusive results. MLPA analysis for KMT2A-PTD is limited to exon 4, whereas NGS and OGM resolved KMT2A-PTD sizes and copy number levels. Conclusions: KMT2A-PTDs are complex gene rearrangements that cannot be fully ascertained using a single genomic platform. MLPA, NGS panels, and OGM are complementary technologies applied in standard-of-care testing for AML patients. MLPA and NGS panels are designed for targeted copy number analysis; however, our results showed that integration of concurrent genomic alterations is needed for accurate KMT2A-PTD identification. Unbalanced chromosomal rearrangements overlapping with KMT2A can interfere with the diagnostic sensitivity and specificity of copy-number-based KMT2A-PTD detection methodologies. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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18 pages, 4006 KiB  
Article
Detection of Genomic Structural Variations Associated with Drug Sensitivity and Resistance in Acute Leukemia
by Darren Finlay, Rabi Murad, Karl Hong, Joyce Lee, Andy Wing Chun Pang, Chi-Yu Lai, Benjamin Clifford, Carol Burian, James Mason, Alex R. Hastie, Jun Yin and Kristiina Vuori
Cancers 2024, 16(2), 418; https://doi.org/10.3390/cancers16020418 - 18 Jan 2024
Viewed by 2657
Abstract
Acute leukemia is a particularly problematic collection of hematological cancers, and, while somewhat rare, the survival rate of patients is typically abysmal without bone marrow transplantation. Furthermore, traditional chemotherapies used as standard-of-care for patients cause significant side effects. Understanding the evolution of leukemia [...] Read more.
Acute leukemia is a particularly problematic collection of hematological cancers, and, while somewhat rare, the survival rate of patients is typically abysmal without bone marrow transplantation. Furthermore, traditional chemotherapies used as standard-of-care for patients cause significant side effects. Understanding the evolution of leukemia to identify novel targets and, therefore, drug treatment regimens is a significant medical need. Genomic rearrangements and other structural variations (SVs) have long been known to be causative and pathogenic in multiple types of cancer, including leukemia. These SVs may be involved in cancer initiation, progression, clonal evolution, and drug resistance, and a better understanding of SVs from individual patients may help guide therapeutic options. Here, we show the utilization of optical genome mapping (OGM) to detect known and novel SVs in the samples of patients with leukemia. Importantly, this technology provides an unprecedented level of granularity and quantitation unavailable to other current techniques and allows for the unbiased detection of novel SVs, which may be relevant to disease pathogenesis and/or drug resistance. Coupled with the chemosensitivities of these samples to FDA-approved oncology drugs, we show how an impartial integrative analysis of these diverse datasets can be used to associate the detected genomic rearrangements with multiple drug sensitivity profiles. Indeed, an insertion in the gene MUSK is shown to be associated with increased sensitivity to the clinically relevant agent Idarubicin, while partial tandem duplication events in the KMT2A gene are related to the efficacy of another frontline treatment, Cytarabine. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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25 pages, 3422 KiB  
Article
Optical Genome Mapping Reveals the Complex Genetic Landscape of Myeloma
by Amélie Giguère, Isabelle Raymond-Bouchard, Vanessa Collin, Jean-Sébastien Claveau, Josée Hébert and Richard LeBlanc
Cancers 2023, 15(19), 4687; https://doi.org/10.3390/cancers15194687 - 22 Sep 2023
Cited by 4 | Viewed by 2595
Abstract
Fluorescence in situ hybridization (FISH) on enriched CD138 plasma cells is the standard method for identification of clinically relevant genetic abnormalities in multiple myeloma. However, FISH is a targeted analysis that can be challenging due to the genetic complexity of myeloma. The aim [...] Read more.
Fluorescence in situ hybridization (FISH) on enriched CD138 plasma cells is the standard method for identification of clinically relevant genetic abnormalities in multiple myeloma. However, FISH is a targeted analysis that can be challenging due to the genetic complexity of myeloma. The aim of this study was to evaluate the potential of optical genome mapping (OGM) to detect clinically significant cytogenetic abnormalities in myeloma and to provide larger pangenomic information. OGM and FISH analyses were performed on CD138-purified cells of 20 myeloma patients. OGM successfully detected structural variants (SVs) (IGH and MYC rearrangements), copy number variants (CNVs) (17p/TP53 deletion, 1p deletion and 1q gain/amplification) and aneuploidy (gains of odd-numbered chromosomes, monosomy 13) classically expected with myeloma and led to a 30% increase in prognosis yield at our institution when compared to FISH. Despite challenges in the interpretation of OGM calls for CNV and aneuploidy losses in non-diploid genomes, OGM has the potential to replace FISH as the standard of care analysis in clinical settings and to efficiently change how we identify prognostic and predictive markers for therapies in the future. To our knowledge, this is the first study highlighting the feasibility and clinical utility of OGM in myeloma. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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17 pages, 2675 KiB  
Article
Clinical Utility of Optical Genome Mapping and 523-Gene Next Generation Sequencing Panel for Comprehensive Evaluation of Myeloid Cancers
by Nikhil Shri Sahajpal, Ashis K. Mondal, Harmanpreet Singh, Ashutosh Vashisht, Sudha Ananth, Daniel Saul, Alex R. Hastie, Benjamin Hilton, Barbara R. DuPont, Natasha M. Savage, Vamsi Kota, Alka Chaubey, Jorge E. Cortes and Ravindra Kolhe
Cancers 2023, 15(12), 3214; https://doi.org/10.3390/cancers15123214 - 16 Jun 2023
Cited by 6 | Viewed by 3479
Abstract
The standard-of-care (SOC) for genomic testing of myeloid cancers primarily relies on karyotyping/fluorescent in situ hybridization (FISH) (cytogenetic analysis) and targeted gene panels (usually ≤54 genes) that harbor hotspot pathogenic variants (molecular genetic analysis). Despite this combinatorial approach, ~50% of myeloid cancer genomes [...] Read more.
The standard-of-care (SOC) for genomic testing of myeloid cancers primarily relies on karyotyping/fluorescent in situ hybridization (FISH) (cytogenetic analysis) and targeted gene panels (usually ≤54 genes) that harbor hotspot pathogenic variants (molecular genetic analysis). Despite this combinatorial approach, ~50% of myeloid cancer genomes remain cytogenetically normal, and the limited sequencing variant profiles obtained from targeted panels are unable to resolve the molecular etiology of many myeloid tumors. In this study, we evaluated the performance and clinical utility of combinatorial use of optical genome mapping (OGM) and a 523-gene next-generation sequencing (NGS) panel for comprehensive genomic profiling of 30 myeloid tumors and compared it to SOC cytogenetic methods (karyotyping and FISH) and a 54-gene NGS panel. OGM and the 523-gene NGS panel had an analytical concordance of 100% with karyotyping, FISH, and the 54-gene panel, respectively. Importantly, the IPSS-R cytogenetic risk group changed from very good/good to very poor in 22% of MDS (2/9) cases based on comprehensive profiling (karyotyping, FISH, and 54-gene panel vs. OGM and 523-gene panel), while additionally identifying six compound heterozygous events of potential clinical relevance in six cases (6/30, 20%). This cost-effective approach of using OGM and a 523-gene NGS panel for comprehensive genomic profiling of myeloid cancers demonstrated increased yield of actionable targets that can potentially result in improved clinical outcomes. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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17 pages, 5703 KiB  
Article
Novel NUP98::ASH1L Gene Fusion in Acute Myeloid Leukemia Detected by Optical Genome Mapping
by Marco Tembrink, Wanda Maria Gerding, Stefan Wieczorek, Thomas Mika, Roland Schroers, Huu Phuc Nguyen, Deepak Ben Vangala and Verena Nilius-Eliliwi
Cancers 2023, 15(11), 2942; https://doi.org/10.3390/cancers15112942 - 27 May 2023
Cited by 8 | Viewed by 2822
Abstract
Optical genome mapping (OGM) recently has demonstrated the potential to improve genetic diagnostics in acute myeloid leukemia (AML). In this study, OGM was utilized as a tool for the detection of genome-wide structural variants and disease monitoring. A previously unrecognized NUP98::ASH1L fusion was [...] Read more.
Optical genome mapping (OGM) recently has demonstrated the potential to improve genetic diagnostics in acute myeloid leukemia (AML). In this study, OGM was utilized as a tool for the detection of genome-wide structural variants and disease monitoring. A previously unrecognized NUP98::ASH1L fusion was detected in an adult patient with secondary AML. OGM identified the fusion of NUP98 to Absent, Small, or Homeotic-Like Histone Lysine Methyltransferase (ASH1L) as result of a complex structural rearrangement between chromosomes 1 and 11. A pipeline for the measurement of rare structural variants (Rare Variant Pipeline, Bionano Genomics, San Diego, CA, USA) was used for detection. As NUP98 and other fusions are relevant for disease classification, this demonstrates the necessity for methods such as OGM for cytogenetic diagnostics in AML. Furthermore, other structural variants showed discordant variant allele frequencies at different time points over the course of the disease and treatment pressure, indicating clonal evolution. These results support OGM to be a valuable tool for primary diagnostics in AML as well as longitudinal testing for disease monitoring and deepening our understanding of genetically heterogenous diseases. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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18 pages, 2310 KiB  
Article
Optical Genome Mapping in Routine Cytogenetic Diagnosis of Acute Leukemia
by Gwendoline Soler, Zangbéwendé Guy Ouedraogo, Carole Goumy, Benjamin Lebecque, Gaspar Aspas Requena, Aurélie Ravinet, Justyna Kanold, Lauren Véronèse and Andrei Tchirkov
Cancers 2023, 15(7), 2131; https://doi.org/10.3390/cancers15072131 - 3 Apr 2023
Cited by 9 | Viewed by 3287
Abstract
Cytogenetic aberrations are found in 65% of adults and 75% of children with acute leukemia. Specific aberrations are used as markers for the prognostic stratification of patients. The current standard cytogenetic procedure for acute leukemias is karyotyping in combination with FISH and RT-PCR. [...] Read more.
Cytogenetic aberrations are found in 65% of adults and 75% of children with acute leukemia. Specific aberrations are used as markers for the prognostic stratification of patients. The current standard cytogenetic procedure for acute leukemias is karyotyping in combination with FISH and RT-PCR. Optical genome mapping (OGM) is a new technology providing a precise identification of chromosomal abnormalities in a single approach. In our prospective study, the results obtained using OGM and standard techniques were compared in 29 cases of acute myeloid (AML) or lymphoblastic leukemia (ALL). OGM detected 73% (53/73) of abnormalities identified by standard methods. In AML cases, two single clones and three subclones were missed by OGM, but the assignment of patients to cytogenetic risk groups was concordant in all patients. OGM identified additional abnormalities in six cases, including one cryptic structural variant of clinical interest and two subclones. In B-ALL cases, OGM correctly detected all relevant aberrations and revealed additional potentially targetable alterations. In T-ALL cases, OGM characterized a complex karyotype in one case and identified additional abnormalities in two others. In conclusion, OGM is an attractive alternative to current multiple cytogenetic testing in acute leukemia that simplifies the procedure and reduces costs. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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12 pages, 3695 KiB  
Article
Optical Genome Mapping as an Alternative to FISH-Based Cytogenetic Assessment in Chronic Lymphocytic Leukemia
by Andriana Valkama, Sandra Vorimo, Timo A. Kumpula, Hannele Räsänen, Eeva-Riitta Savolainen, Katri Pylkäs and Tuomo Mantere
Cancers 2023, 15(4), 1294; https://doi.org/10.3390/cancers15041294 - 17 Feb 2023
Cited by 10 | Viewed by 3751
Abstract
The fluorescence in situ hybridization (FISH) technique plays an important role in the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented with other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, [...] Read more.
The fluorescence in situ hybridization (FISH) technique plays an important role in the risk stratification and clinical management of patients with chronic lymphocytic leukemia (CLL). For genome-wide analysis, FISH needs to be complemented with other cytogenetic methods, including karyotyping and/or chromosomal microarrays. However, this is often not feasible in a diagnostic setup. Optical genome mapping (OGM) is a novel technique for high-resolution genome-wide detection of structural variants (SVs), and previous studies have indicated that OGM could serve as a generic cytogenetic tool for hematological malignancies. Herein, we report the results from our study evaluating the concordance of OGM and standard-of-care FISH in 18 CLL samples. The results were fully concordant between these two techniques in the blinded comparison. Using in silico dilution series, the lowest limit of detection with OGM was determined to range between 3 and 9% variant allele fractions. Genome-wide analysis by OGM revealed additional (>1 Mb) aberrations in 78% of the samples, including both unbalanced and balanced SVs. Importantly, OGM also enabled the detection of clinically relevant complex karyotypes, undetectable by FISH, in three samples. Overall, this study demonstrates the potential of OGM as a first-tier cytogenetic test for CLL and as a powerful tool for genome-wide SV analysis. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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21 pages, 3986 KiB  
Article
Optical Genome Mapping: A Promising New Tool to Assess Genomic Complexity in Chronic Lymphocytic Leukemia (CLL)
by Anna Puiggros, Silvia Ramos-Campoy, Joanna Kamaso, Mireia de la Rosa, Marta Salido, Carme Melero, María Rodríguez-Rivera, Sandrine Bougeon, Rosa Collado, Eva Gimeno, Rocío García-Serra, Sara Alonso, Marco Antonio Moro-García, María Dolores García-Malo, Xavier Calvo, Leonor Arenillas, Ana Ferrer, Tuomo Mantere, Alexander Hoischen, Jacqueline Schoumans and Blanca Espinetadd Show full author list remove Hide full author list
Cancers 2022, 14(14), 3376; https://doi.org/10.3390/cancers14143376 - 11 Jul 2022
Cited by 22 | Viewed by 3848
Abstract
Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules [...] Read more.
Novel treatments in chronic lymphocytic leukemia (CLL) have generated interest regarding the clinical impact of genomic complexity, currently assessed by chromosome banding analysis (CBA) and chromosomal microarray analysis (CMA). Optical genome mapping (OGM), a novel technique based on imaging of long DNA molecules labeled at specific sites, allows the identification of multiple cytogenetic abnormalities in a single test. We aimed to determine whether OGM is a suitable alternative to cytogenomic assessment in CLL, especially focused on genomic complexity. Cytogenomic OGM aberrations from 42 patients were compared with CBA, FISH, and CMA information. Clinical–biological characteristics and time to first treatment (TTFT) were analyzed according to the complexity detected by OGM. Globally, OGM identified 90.3% of the known alterations (279/309). Discordances were mainly found in (peri-)centromeric or telomeric regions or subclonal aberrations (<15–20%). OGM underscored additional abnormalities, providing novel structural information on known aberrations in 55% of patients. Regarding genomic complexity, the number of OGM abnormalities had better accuracy in predicting TTFT than current methods (C-index: 0.696, 0.602, 0.661 by OGM, CBA, and CMA, respectively). A cut-off of ≥10 alterations defined a complex OGM group (C-OGM, n = 12), which included 11/14 patients with ≥5 abnormalities by CBA/CMA and one patient with chromothripsis (Kappa index = 0.778; p < 0.001). Moreover, C-OGM displayed enrichment of TP53 abnormalities (58.3% vs. 3.3%, p < 0.001) and a significantly shorter TTFT (median: 2 vs. 43 months, p = 0.014). OGM is a robust technology for implementation in the routine management of CLL patients, although further studies are required to define standard genomic complexity criteria. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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20 pages, 2782 KiB  
Article
Optical Genome Mapping as a Diagnostic Tool in Pediatric Acute Myeloid Leukemia
by Julia Suttorp, Jonathan Lukas Lühmann, Yvonne Lisa Behrens, Gudrun Göhring, Doris Steinemann, Dirk Reinhardt, Nils von Neuhoff and Markus Schneider
Cancers 2022, 14(9), 2058; https://doi.org/10.3390/cancers14092058 - 19 Apr 2022
Cited by 18 | Viewed by 4082
Abstract
Pediatric AML is characterized by numerous genetic aberrations (chromosomal translocations, deletions, insertions) impacting its classification for risk of treatment failure. Aberrations are described by classical cytogenetic procedures (karyotyping, FISH), which harbor limitations (low resolution, need for cell cultivation, cost-intensiveness, experienced staff required). Optical [...] Read more.
Pediatric AML is characterized by numerous genetic aberrations (chromosomal translocations, deletions, insertions) impacting its classification for risk of treatment failure. Aberrations are described by classical cytogenetic procedures (karyotyping, FISH), which harbor limitations (low resolution, need for cell cultivation, cost-intensiveness, experienced staff required). Optical Genome Mapping (OGM) is an emerging chip-based DNA technique combining high resolution (~500 bp) with a relatively short turnaround time. Twenty-four pediatric patients with AML, bi-lineage leukemia, and mixed-phenotype acute leukemia were analyzed by OGM, and the results were compared with cytogenetics. Results were discrepant in 17/24 (70%) cases, including 32 previously unknown alterations called by OGM only. One newly detected deletion and two translocations were validated by primer walking, breakpoint-spanning PCR, and DNA sequencing. As an added benefit, in two cases, OGM identified a new minimal residual disease (MRD) marker. Comparing impact on risk stratification in de novo AML, 19/20 (95%) cases had concordant results while only OGM unraveled another high-risk aberration. Thus, OGM considerably expands the methodological spectrum to optimize the diagnosis of pediatric AML via the identification of new aberrations. Results will contribute to a better understanding of leukemogenesis in pediatric AML. In addition, aberrations identified by OGM may provide markers for MRD monitoring. Full article
(This article belongs to the Special Issue Optical Genome Mapping in Hematological Malignancies)
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