Přehled o publikaci

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults in the Western world. It is characterized by a highly variable clinical course. In patients with an unfavorable prognosis, a complex karyotype (CK) is recurrently observed, defined by the presence of ≥3 chromosomal alterations, including numerical and structural variants (SVs). We hypothesize that precise characterization of complex SVs may contribute to understanding the molecular mechanisms driving disease progression and aid in selecting appropriate therapy. Chromosomal alterations in CLL are primarily detected using G-banding, FISH, and mFISH, which do not provide information on DNA sequence or chromatin interactions and have limited resolution. Modern technologies, such as short-read (Illumina) and long-read sequencing (e.g., Oxford Nanopore Technologies; ONT), chromatin conformation analysis (Hi-C), and optical genome mapping (OGM; Bionano Genomics), offer a more comprehensive, high-resolution view of the entire genome. We performed a comparative analysis of data from these routine and advanced methods in 10 CLL patients with CK. Structural variants from ONT data were identified using an intersection of the tools SVIM, Sniffles, and Delly, while Illumina data were analyzed using Delly and Manta. For analyzing SVs detected by OGM, the Rare Variant Analysis approach was applied, and for detecting aberrations using Hi-C, the tools EagleC and NeoLoopFinder were utilized. A visual comparison of results will be presented for a selected sample. The potential outputs of each method will be demonstrated, and the advantages and limitations of each approach will be assessed. Based on our findings, we believe that advanced genome analysis, in combination with traditional approaches, holds great promise for addressing complex chromosomal rearrangements, not only in CLL.