Lühmann Jonathan Lukas, Stelter Marie, Wolter Marie, Kater Josephine, Lentes Jana, Bergmann Anke Katharina, Schieck Maximilian, Göhring Gudrun, Möricke Anja, Cario Gunnar, Žaliová Markéta, Schrappe Martin, Schlegelberger Brigitte, Stanulla Martin, Steinemann Doris
Department of Human Genetics, Hannover Medical School, 30625 Hannover, Germany.
Department of Pediatrics I, ALL-BFM Study Group, Christian-Albrechts University Kiel and University Medical Center Schleswig-Holstein, 24105 Kiel, Germany.
Cancers (Basel). 2021 Aug 30;13(17):4388. doi: 10.3390/cancers13174388.
Acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer occurring in children. ALL is characterized by structural and numeric genomic aberrations that strongly correlate with prognosis and clinical outcome. Usually, a combination of cyto- and molecular genetic methods (karyotyping, array-CGH, FISH, RT-PCR, RNA-Seq) is needed to identify all aberrations relevant for risk stratification. We investigated the feasibility of optical genome mapping (OGM), a DNA-based method, to detect these aberrations in an all-in-one approach. As proof of principle, twelve pediatric ALL samples were analyzed by OGM, and results were validated by comparing OGM data to results obtained from routine diagnostics. All genomic aberrations including translocations (e.g., dic(9;12)), aneuploidies (e.g., high hyperdiploidy) and copy number variations (e.g., , ) known from other techniques were also detected by OGM. Moreover, OGM was superior to well-established techniques for resolution of the more complex structure of a translocation t(12;21) and had a higher sensitivity for detection of copy number alterations. Importantly, a new and unknown gene fusion of and due to a translocation t(9;11) was detected. We demonstrate the feasibility of OGM to detect well-established as well as new putative prognostic markers in an all-in-one approach in ALL. We hope that these limited results will be confirmed with testing of more samples in the future.
急性淋巴细胞白血病（ALL）是儿童中最常见的癌症类型。ALL的特征是基因组结构和数量异常，这些异常与预后和临床结果密切相关。通常，需要结合细胞遗传学和分子遗传学方法（核型分析、阵列比较基因组杂交、荧光原位杂交、逆转录聚合酶链反应、RNA测序）来识别所有与风险分层相关的异常。我们研究了基于DNA的光学基因组图谱（OGM）以一体化方法检测这些异常的可行性。作为原理验证，通过OGM对12份儿童ALL样本进行了分析，并通过将OGM数据与常规诊断结果进行比较来验证结果。OGM还检测到了所有基因组异常，包括其他技术已知的易位（例如，dic(9;12)）、非整倍体（例如，高超二倍体）和拷贝数变异（例如， ， ）。此外，在解析更复杂的易位t(12;21)结构方面，OGM优于成熟技术，并且在检测拷贝数改变方面具有更高的灵敏度。重要的是，检测到了由于易位t(9;11)导致的 和 的一种新的未知基因融合。我们证明了OGM以一体化方法在ALL中检测既定的以及新的潜在预后标志物的可行性。我们希望这些有限的结果在未来通过检测更多样本得到证实。
