College of Life Sciences and Bioengineering, School of Physical Science and Engineering, Beijing Jiaotong University.
Hematology Center, Beijing Children's Hospital, Capital Medical University; National Center for Children's Health.
J Pediatr Hematol Oncol. 2024 Jan 1;46(1):e71-e82. doi: 10.1097/MPH.0000000000002787. Epub 2023 Nov 29.
Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM.
OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L :: AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR.
In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L :: AHI1 and GRIK1::NSDHL , which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction.
Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.
准确的组织学和分子遗传学诊断对于儿科淋巴细胞性淋巴瘤（LBL）患者的发病机制研究至关重要。光学基因组图谱（OGM）作为一种一体化的过程，可以检测到大多数主要的基因组风险标记物，这解决了传统细胞遗传学检测的一些局限性，例如分辨率和通量低、难以确定基因组定位、以及在重复、倒位和插入中确定片段的方向。在这里，我们首次使用 OGM 检查了 5 例 LBL 患儿的细胞遗传学。
使用 OGM 分析了根据改良 NHL-BFM95 骨干方案治疗的 5 例小儿 LBL 患者的样本。使用全外显子组测序（WES）在 MGI Tech（DNBSEQ-T7）平台上确认 OGM 识别的具有潜在临床意义的结构变异（SVs）的存在。根据 WES 揭示的融合外显子序列，通过 cDNA 为基础的 PCR 扩增了 4 号病例中的 HBS1L::AHI1 融合 mRNA。
OGM 总共鉴定出 251 个罕见变异（67 个插入、129 个缺失、3 个倒位、25 个重复、15 个染色体内易位和 12 个染色体间易位）和 229 个拷贝数变异（203 个增益和 26 个丢失）。除了传统细胞遗传学技术检测到的所有可重现和具有病理意义的基因组 SVs 外，OGM 还鉴定出了更多具有明确或潜在病理意义的 SVs，这些 SVs未被传统方法检测到，包括 2 个新的融合基因 HBS1L::AHI1 和 GRIK1::NSDHL，这些基因通过 WES 和/或逆转录-聚合酶链反应得到了证实。
我们的结果表明，OGM 检测基因组异常是可行的，这些异常可能作为一个重要的驱动因素，在淋巴瘤发生和发展中发挥重要作用。
