Valkama Andriana, Vorimo Sandra, Kumpula Timo A, Räsänen Hannele, Savolainen Eeva-Riitta, Pylkäs Katri, Mantere Tuomo
Laboratory of Cancer Genetics and Tumor Biology, Translational Medicine Research Unit and Biocenter Oulu, University of Oulu, 90220 Oulu, Finland.
Northern Finland Laboratory Centre Nordlab, 90220 Oulu, Finland.
Cancers (Basel). 2023 Feb 17;15(4):1294. doi: 10.3390/cancers15041294.
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.
荧光原位杂交（FISH）技术在慢性淋巴细胞白血病（CLL）患者的风险分层和临床管理中发挥着重要作用。对于全基因组分析，FISH需要与其他细胞遗传学方法相结合，包括核型分析和/或染色体微阵列分析。然而，在诊断过程中这往往不可行。光学基因组图谱（OGM）是一种用于高分辨率全基因组检测结构变异（SV）的新技术，先前的研究表明OGM可作为血液系统恶性肿瘤的通用细胞遗传学工具。在此，我们报告了一项研究结果，该研究评估了18例CLL样本中OGM与标准护理FISH的一致性。在盲法比较中，这两种技术的结果完全一致。通过计算机模拟稀释系列，确定OGM的最低检测限在3%至9%的变异等位基因分数之间。OGM进行的全基因组分析显示，78%的样本存在额外的（>1 Mb）畸变，包括不平衡和平衡的SV。重要的是，OGM还在三个样本中检测到了FISH无法检测到的临床相关复杂核型。总体而言，本研究证明了OGM作为CLL的一线细胞遗传学检测方法以及全基因组SV分析的强大工具的潜力。
