Optical Genome Mapping in Routine Cytogenetic Diagnosis of Acute Leukemia

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. 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.

Optical Genome Mapping Identifies Novel Recurrent Structural Alterations in Childhood ETV6::RUNX1+ and High Hyperdiploid Acute Lymphoblastic Leukemia

“…Around 20% of leukemic blasts are required for SNP‐array in a diagnostic setting for large CN alterations 34 , 35 . Our study and others 14 , 36 , 37 showed that OGM performance on samples with blast amounts of about 20%–30% could also detect alterations observed by conventional diagnostic methods. Hence, OGM could be an attractive option for routine diagnostic workup of hematological malignancies, as it has a fast turnaround time of ≈5 days from sample acquisition to data analysis.…”

Comparison of Optical Genome Mapping With Conventional Diagnostic Methods for Structural Variant Detection in Hematologic Malignancies

“…Highly repetitive regions, such as centromeric regions, short arms of acrocentric chromosomes, pseudo-autosomal regions (PARs), and telomeric regions, are often poorly covered by OGM because of missing labels and unreliable reference map data. Consequently, OGM may fail to detect SVs involving these regions, a well-known limitation [ 14 - 17 ]. However, as these regions may contain clinically relevant SVs, efforts should be undertaken to identify recurrent SVs in these areas.…”

“…We analyzed OGM results of diagnostic samples from patients with hematologic malignancies and evaluated their concordance with the results of conventional methods in detecting SVs. Several recent studies have assessed the clinical usefulness of SV detection using OGM in patients with blood cancer [13][14][15][16][17][18][19][20][21]. These studies mainly used CBA, FISH, RT-PCR, CMA, or MLPA as conventional methods for comparison.…”

DNA Quantity and Quality Comparisons between Cryopreserved and FFPE Tumors from Matched Pan-Cancer Samples

“…This is becoming increasingly important in newer technologies that depend on high molecular weight DNA for analysis, such as long-read sequencing and optical genome mapping [8,18]. Protocols for these applications can generate even longer DNA fragments ranging from 30 kb to 2000 kb [19][20][21]. High molecular weight DNA allows for more precise detection of large structural variants that are often associated with tumors that are genomically unstable [9,22].…”