Department of Hematology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, P.R. China.
Hainan General Hospital, University of South China, Haikou, Hainan, China.
Mol Genet Genomic Med. 2020 Sep;8(9):e1369. doi: 10.1002/mgg3.1369. Epub 2020 Jul 7.
Despite targeted sequencing have identified several mutations for leukemia, there is still a limit of mutation screening for Chinese leukemia. Here, we used targeted next-generation sequencing for testing the mutation patterns of Chinese leukemia patients.
We performed targeted sequencing of 504 tumor-related genes in 109 leukemia samples to identify single-nucleotide variants (SNVs) and insertions and deletions (INDELs). Pathogenic variants were assessed based on the American College of Medical Genetics and Genomics (ACMG) guidelines. The functional impact of pathogenic genes was explored through gene ontology (GO), pathway analysis, and protein-protein interaction network in silico.
We identified a total of 4,655 SNVs and 614 INDELs in 419 genes, in which PDE4DIP, NOTCH2, FANCA, BCR, and ROS1 emerged as the highly mutated genes. Of note, we were the first to demonstrate an association of PDE4DIP mutation and leukemia. Based on ACMG guidelines, 39 pathogenic and likely pathogenic mutations in 27 genes were found. GO annotation showed that the biological process including gland development, leukocyte differentiation, respiratory system development, myeloid leukocyte differentiation, mesenchymal to epithelial transition, and so on were involved.
Our study provided a map of gene mutations in Chinese patients with leukemia and gave insights into the molecular pathogenesis of leukemia.
尽管靶向测序已经确定了几种白血病的突变，但对中国白血病的突变筛查仍存在局限性。在这里，我们使用靶向下一代测序来测试中国白血病患者的突变模式。
我们对 109 个白血病样本中的 504 个肿瘤相关基因进行了靶向测序，以鉴定单核苷酸变异（SNVs）和插入/缺失（INDELs）。根据美国医学遗传学与基因组学学院（ACMG）指南评估致病性变异。通过基因本体论（GO）、通路分析和计算机中的蛋白质-蛋白质相互作用网络，探讨致病性基因的功能影响。
我们在 419 个基因中总共鉴定出 4655 个 SNVs 和 614 个 INDELs，其中 PDE4DIP、NOTCH2、FANCA、BCR 和 ROS1 是高度突变的基因。值得注意的是，我们首次证明 PDE4DIP 突变与白血病有关。根据 ACMG 指南，在 27 个基因中发现了 39 个致病性和可能致病性突变。GO 注释表明，生物学过程包括腺体发育、白细胞分化、呼吸系统发育、髓样白细胞分化、间质到上皮转化等。
我们的研究提供了中国白血病患者基因突变图谱，并深入了解了白血病的分子发病机制。
