Feasibility of Optical Genome Mapping in Cytogenetic Diagnostics of Hematological Neoplasms: A New Way to Look at DNA

Abstract

Optical genome mapping (OGM) is a new genome-wide technology that can reveal both structural genomic variations (SVs) and copy number variations (CNVs) in a single assay. OGM was initially employed to perform genome assembly and genome research, but it is now more widely used to study chromosome aberrations in genetic disorders and in human cancer. One of the most useful OGM applications is in hematological malignancies, where chromosomal rearrangements are frequent and conventional cytogenetic analysis alone is insufficient, necessitating further confirmation using ancillary techniques such as fluorescence in situ hybridization, chromosomal microarrays, or multiple ligation-dependent probe amplification. The first studies tested OGM efficiency and sensitivity for SV and CNV detection, comparing heterogeneous groups of lymphoid and myeloid hematological sample data with those obtained using standard cytogenetic diagnostic tests. Most of the work based on this innovative technology was focused on myelodysplastic syndromes (MDSs), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL), whereas little attention was paid to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), and none was paid to lymphomas. The studies showed that OGM can now be considered as a highly reliable method, concordant with standard cytogenetic techniques but able to detect novel clinically significant SVs, thus allowing better patient classification, prognostic stratification, and therapeutic choices in hematological malignancies.

Genomic technologies for detecting structural variations in hematologic malignancies

“…OGM is a new genomic technology that can reveal SVs, CNVs, and whole-chromosome aneuploidies in a single experiment [ 13 ]. OGM electrophoreses ultra-long high-molecular-weight DNA (> 150 kb) into nanochannels, linearizing them for imaging, and creates a consensus genome map from the processed images [ 13 ].…”

“…OGM is a new genomic technology that can reveal SVs, CNVs, and whole-chromosome aneuploidies in a single experiment [ 13 ]. OGM electrophoreses ultra-long high-molecular-weight DNA (> 150 kb) into nanochannels, linearizing them for imaging, and creates a consensus genome map from the processed images [ 13 ]. Recent studies have highlighted the advantages of OGM as an emerging genomic technology for hematologic malignancies, which can potentially replace conventional cytogenetic diagnostics [ 13 – 15 , 55 – 60 ].…”

“…The use of next-generation sequencing (NGS) technologies can facilitate the sensitive and accurate detection of many common gene rearrangements and has emerged as an alternative to RT-PCR and FISH for detecting pathogenic fusion genes in hematologic malignancies [ 1 , 10 – 12 ]. More recently, other novel genome-wide technologies, such as optical genome mapping (OGM) technology, have emerged [ 13 – 15 ].…”

Optical Genome Mapping as a Tool to Unveil New Molecular Findings in Hematological Patients with Complex Chromosomal Rearrangements

“…Also known as "Next Generation Cytogenetics", this method exploits DNA labeling rather than sequencing and is considered a link between techniques based on sequencing and whole chromosome analysis [11][12][13]. Several studies have tested this technology to identify genomic aberrations in both constitutional syndromes and tumors [12,14], demonstrating that OGM is particularly effective in defining complex genomic rearrangements [13,15] such as chromothripsis, consisting of hundreds of genomic rearrangements caused by the shattering of a chromosome and the random reassembly of the generated genomic fragments [16][17][18]. Considering these peculiarities, OGM is frequently applied to the study of hematological diseases, where complex karyotypes are frequent and conventional cytogenetic analysis alone is insufficient.…”

Optical Genome Mapping for Cryptic Chromosomal Rearrangements Identification in Clinical Practice

“…3,4 A growing number of studies have recently demonstrated the efficiency and superiority of OGM in various clinical settings, including both prenatal and postnatal congenital conditions, as well as various hematological and other malignancies. [5][6][7] Here, we explore the value of OGM in identifying cryptic BCRs using a case series from our clinical practice. This study was approved by the ethics committee of the Nanjing Drum Tower Hospital affiliated with Nanjing University Medical School (no.…”