Institute of Statistical Science Academia Sinica, 128 Academia Road, Section 2, Nankang, Taipei, 11529, Taiwan.
Departments of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Sci Rep. 2021 Jan 12;11(1):769. doi: 10.1038/s41598-020-80613-6.
T-cell acute lymphoblastic leukemia (T-ALL) is caused by the accumulation of multiple genetic alterations. To determine the frequency of common genetic mutations and possible prognostic markers in childhood T-ALL, we performed targeted sequencing of 67 genes across 64 cases treated according to Taiwan Pediatric Oncology Group protocols between January 2002 and December 2015. Together, 302 variants were identified in 60 genes including 233 single nucleotide variants and 69 indels. Sixty-four samples had a median number of six genetic lesions each (range 1-17). Thirteen genes had mutation frequencies > 10%, and 5 were > 20%, with the highest being NOTCH1 (70.31%). Protocadherins FAT1 (32.81%) and FAT3 (17.19%), and the ubiquitin ligase component FBXW7 (28.13%) had higher mutation frequencies than previously reported. Other mutation frequencies (PHF6, DNM2, DNMT3A, CNOT3, and WT1) were within previously reported ranges. Three epigenetic-related genes (KMT2D, DNMT3A, and EZH2) were mutated in our cohort. JAK-STAT signaling pathway genes had mutation frequencies of 3-13% and were observed in 23 cases (35.94%). Changes to genes in the ErbB signaling pathway were detected in 20 cases (31.25%). Patients with NOTCH1/FBXW7 mutations and RAS/PTEN germline exhibited better 5-year overall survival rates.
T 细胞急性淋巴细胞白血病（T-ALL）是由多种遗传改变的积累引起的。为了确定儿童 T-ALL 中常见遗传突变和可能的预后标志物的频率，我们对根据台湾儿科肿瘤组方案于 2002 年 1 月至 2015 年 12 月治疗的 64 例患者进行了 67 个基因的靶向测序。总共在 60 个基因中鉴定出 302 个变体，包括 233 个单核苷酸变体和 69 个插入缺失。64 个样本的每个样本的中位数有 6 个遗传病变（范围为 1-17）。13 个基因的突变频率>10%，5 个基因的突变频率>20%，最高的是 NOTCH1（70.31%）。原钙黏蛋白 FAT1（32.81%）和 FAT3（17.19%）以及泛素连接酶成分 FBXW7（28.13%）的突变频率高于之前报道的频率。其他突变频率（PHF6、DNM2、DNMT3A、CNOT3 和 WT1）处于之前报道的范围内。我们的队列中有 3 个表观遗传学相关基因（KMT2D、DNMT3A 和 EZH2）发生了突变。JAK-STAT 信号通路基因的突变频率为 3-13%，在 23 例患者（35.94%）中观察到。在 20 例患者（31.25%）中检测到 ErbB 信号通路基因的变化。具有 NOTCH1/FBXW7 突变和 RAS/PTEN 种系的患者具有更好的 5 年总生存率。
