On Day 2 of Bionano Genomics 2022 Symposium, world-leading experts discussed the application of optical genome mapping (OGM) in hematologic malignancies.
Over the past decade, molecular profiling has become key to understanding genomic alterations in hematologic malignancies, which in turn leads to efficient clinical translation. Genomics is now the cornerstone of precision care in hematologic malignancies, using a variety of techniques including karyotyping, fluorescent in situ hybridization (FISH), chromosomal microarray (CMA), and more recently, next-generation sequencing (NGS). Early single gene testing has evolved into multigene panels, and whole-genome, transcriptome, and exome testing as part of clinical care.
While these traditional techniques are powerful, they also have specific limitations. Karyotyping is still considered gold standard but has low resolution (5 Mb). CMA has higher resolution but cannot detect balanced structural aberrations and smaller copy number variations. NGS techniques are highly sensitive and effective for detection of single-base mutations but are limited in their ability to detect structural variants and copy number variations. To overcome the individual limitations of existing methods, a sequential testing cascade is typically used. While this approach can provide good coverage across variant categories, it is time-consuming, expensive, requires a larger amount of cancer samples, and makes analyses and interpretation cumbersome and error prone.
OGM brings significant value over all traditional techniques. Serving as a structural variation discovery workflow, it provides 1600X coverage of the human genome and can detect structural variations as low as 1% allele fraction. Importantly, OGM can consolidate traditional assays into one, while also identifying novel variants that may become useful for patient stratification or targeted therapeutics. On Day 2 of the 2022 Virtual Symposium, scientific experts discussed their experiences using OGM in different hematologic malignancies and showed data demonstrating the superiority of OGM over traditional techniques and their combinations as well.
OGM characterizes known and novel genetic aberrations in B-cell Chronic Lymphocytic Leukemia (B-CLL) and Acute Lymphoblastic Leukemias (ALL). B-CLL is the most common form of adult leukemia. Karyotyping and FISH panels for characterized genetic aberrations are typically used in the evaluation of B-CLL. Dr. Saurabh Gupta from Quest Diagnostics has focused his initial evaluation of OGM on this malignancy and shared the overall high concordance of OGM with traditional methods to detect known gene rearrangements in B-CLL. Importantly, he also described cases in which OGM identified variants that were missed or not fully characterized by conventional methods but were of potential prognostic value. Dr. Anna Puiggros from Hospital del Mar in Barcelona, Spain similarly found OGM to effectively detect genetic aberrations and several additional abnormalities in chronic lymphocytic leukemia (CLL) samples in an independent study.
OGM is faster and more cost effective than traditional techniques for analyzing ALL. In two independent studies, Jonathan L. Lühmann, from Hannover Medical School, Germany and Dr. Barbara Dewaele, from University Hospitals, Leuven found that OGM reliably and cost-effectively identified genetic markers when compared to traditional panels for acute lymphoblastic leukemia (ALL). ALLs are hematopoietic neoplasms of lymphoid precursors, characterized by the accumulation of malignant, immature lymphoid cells in the bone marrow and blood. The classic panel for these types of neoplasms includes karyotyping, FISH, and multiplex ligation-dependent probe amplification (MLPA). In addition to accurately identifying all translocations, OGM also detected additional potentially targetable new fusions and chromothripsis. Additionally, Dr. Adrian Dubuc presented a case study of a 37-year-old veteran who was diagnosed as Philadelphia-negative B-ALL. Based on a battery of cytogenetics tests, this patient was found to have a complex genetic profile. Using OGM alone, Dr. Dubuc and his team were able to confirm this same complex profile.
OGM detects more clinically relevant variants across a wide range of hematologic malignancies including acute myeloid leukemia (AML). Other presenters shared study results evaluating the OGM workflow for a variety of different hematologic malignancies. Dr. Kornelia Neveling has set out to determine whether OGM could replace traditional tests such as karyotyping and FISH and is conducting a clinical utility study for subjects with acute myeloid leukemia (AML). The interim analyses for this study are promising. Data from similar comparative analyses were presented by Bence Dvorak on plasma cell discrasias, Dr. Elena Garcia Sanchez on pediatric leukemias, Dr. Brynn Levy for acute myelogenous leukemia (AML), and Dr. Adam Smith on multiple malignancy types. The overall conclusions from these independent studies are that OGM can detect known and novel genetic aberrations, it can facilitate interpretation and reporting, and can reduce time from procuring the sample to reporting data.
“We continue to be impressed by the work of our colleagues, and grateful for their contributions to genetic discovery in cancer,” remarked Alka Chaubey, PhD, FACMG, chief medical officer of Bionano Genomics. “We’re excited by the opportunity for OGM to identify new variants that may directly impact the lives of people living with leukemia and related conditions.”
Bence Dvorak, MSc
Oncology laboratory, University Children’s Hospital Zurich – Eleonore Foundation, Switzerland
“Characterization of Plasma Cell Discrasias by Optical Genome Mapping”
Jonathan L. Lühmann, MSc
PhD candidate in Molecular Medicine, Hannover Medical School, Germany
“The Clinical Utility of Optical Genome Mapping for the Assessment of Genomic Aberrations in Acute Lymphoblastic Leukemia”
Anna Puiggros, PhD
Assistant Biologist, Hospital del Mar in Barcelona, Spain
“The hidden side of genomic complexity: learning from OGM in chronic lymphocytic leukemia”
Barbara Dewaele, PhD
Laboratory Geneticist, University Hospitals, Leuven
“Opportunities of Optical Genome Mapping for Genetic Diagnosis in Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia”
Kornelia Neveling, PhD
Translational Genomics researcher, Radboud University Medical Center, Nijmegen, The Netherlands
“Technical and clinical validation of optical genome mapping @RadboudUMC”
Elena Garcia Sanchez, PhD
Researcher, Hospital Infantil Universitario Niño Jesús in Madrid, Spain
“Optical Genome Mapping for Diagnosis of Paediatric Leukaemia”
Brynn Levy, MSc (Med), PhD, FACMG
Professor of Pathology & Cell Biology, Columbia University Medical Center, New York, USA
“Assessing Genomic Aberrations in AML using Optical Genome Mapping: Insights from a National Multi-Center Study”
Adrian Dubuc, PhD, FACMG
Assistant Director of Cytogenetics, Brigham and Women’s Hospital, and Assistant Professor at Harvard Medical School, Massachusetts, USA
“Shining a New Light on Cancer Cytogenetics: Leveraging Novel Technological Approaches for Improved Understanding in B-ALL”
Adam Smith, MSc, PhD, FCCMG, FACMG, erCLG
Director of Cancer Cytogenetics at the University Health Network in Toronto, Ontario, Canada
“A Year in Review: Parallel Testing of Hematologic Malignancies using Optical Genome Mapping Compared to Conventional Cytogenetics.”
Saurabh Gupta, PhD, DABMGG
Chief Director, Quest Diagnostics, Texas, USA
“Optical genome mapping: utility for stratification of B-CLL by accurate identification of clinically relevant structural variants.”
Symposium presentations will be available online after January 14, 2022 at