Department of Laboratory Medicine, Mokpo Jung Ang Hospital, Mokpo, Korea.
Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea.
Sci Rep. 2021 Apr 26;11(1):8893. doi: 10.1038/s41598-021-88449-4.
In addition to somatic mutations, germline genetic predisposition to hematologic malignancies is currently emerging as an area attracting high research interest. In this study, we investigated genetic alterations in Korean acute lymphoblastic leukemia/lymphoma (ALL) patients using targeted gene panel sequencing. To this end, a gene panel consisting of 81 genes that are known to be associated with 23 predisposition syndromes was investigated. In addition to sequence variants, gene-level copy number variations (CNVs) were investigated as well. We identified 197 somatic sequence variants and 223 somatic CNVs. The IKZF1 alteration was found to have an adverse effect on overall survival (OS) and relapse-free survival (RFS) in childhood ALL. We found recurrent somatic alterations in Korean ALL patients similar to previous studies on both prevalence and prognostic impact. Six patients were found to be carriers of variants in six genes associated with primary immunodeficiency disorder (PID). Of the 81 genes associated with 23 predisposition syndromes, this study found only one predisposition germline mutation (TP53) (1.1%). Altogether, our study demonstrated a low probability of germline mutation predisposition to ALL in Korean ALL patients.
除了体细胞突变外，目前生殖系遗传易感性与血液系统恶性肿瘤也成为了一个备受关注的研究领域。在这项研究中，我们使用靶向基因panel 测序方法研究了韩国急性淋巴细胞白血病/淋巴瘤（ALL）患者的遗传改变。为此，我们研究了一个包含 81 个基因的基因panel，这些基因与 23 种易感性综合征有关。除了序列变异，我们还研究了基因水平的拷贝数变异（CNVs）。我们鉴定了 197 个体细胞序列变异和 223 个体细胞 CNVs。IKZF1 改变被发现对儿童 ALL 的总生存期（OS）和无复发生存期（RFS）有不良影响。我们发现韩国 ALL 患者的体细胞改变与之前的研究在普遍性和预后影响方面相似。在 6 名患者中发现了与原发性免疫缺陷疾病（PID）相关的 6 个基因的变异携带者。在与 23 种易感性综合征相关的 81 个基因中，本研究仅发现了一个易感性种系突变（TP53）（1.1%）。总的来说，我们的研究表明韩国 ALL 患者的 ALL 种系突变易感性概率较低。
