Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia.
Targeted sequencing to identify genetic alterations and prognostic markers in pediatric T-cell acute lymphoblastic leukemia.
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DOI：
10.1038/s41598-020-80613-6
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发表时间：
2021-01-12
影响因子：
4.6
通讯作者：
Yang YL
中科院分区：
文献类型：
--
作者：
Chang YH;Yu CH;Jou ST;Lin CY;Lin KH;Lu MY;Wu KH;Chang HH;Lin DT;Lin SW;Chen HY;Yang YL
T 细胞急性淋巴细胞白血病 (T-ALL) 是由多种基因改变累积引起的。为了确定儿童 T-ALL 中常见基因突变的频率和可能的预后标志物，我们对 2002 年 1 月至 2015 年 12 月期间根据台湾儿童肿瘤小组方案治疗的 64 例病例的 67 个基因进行了靶向测序。在 60 个基因中总共鉴定了 302 个变异，包括 233 个单核苷酸变异和 69 个插入缺失。 64 个样本中每个样本有 6 个遗传损伤（范围 1-17）。突变频率≥10%的基因有13个，≥20%的基因有5个，其中最高的是NOTCH1（70.31%）。原钙粘蛋白 FAT1 (32.81%) 和 FAT3 (17.19%) 以及泛素连接酶成分 FBXW7 (28.13%) 的突变频率比之前报道的要高。其他突变频率（PHF6、DNM2、DNMT3A、CNOT3 和 WT1）均在先前报告的范围内。我们的队列中三个表观遗传相关基因（KMT2D、DNMT3A 和 EZH2）发生突变。 JAK-STAT信号通路基因突变频率为3%~13%，共23例（35.94%）。 20例（31.25%）检测到ErbB信号通路基因变化。具有 NOTCH1/FBXW7 突变和 RAS/PTEN 种系的患者表现出更好的 5 年总体生存率。
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.
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影响因子：
30.8
作者：
Liu Y;Easton J;Shao Y;Maciaszek J;Wang Z;Wilkinson MR;McCastlain K;Edmonson M;Pounds SB;Shi L;Zhou X;Ma X;Sioson E;Li Y;Rusch M;Gupta P;Pei D;Cheng C;Smith MA;Auvil JG;Gerhard DS;Relling MV;Winick NJ;Carroll AJ;Heerema NA;Raetz E;Devidas M;Willman CL;Harvey RC;Carroll WL;Dunsmore KP;Winter SS;Wood BL;Sorrentino BP;Downing JR;Loh ML;Hunger SP;Zhang J;Mullighan CG
通讯作者：
Mullighan CG
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
2.6
作者：
Inaba, Hiroto;Azzato, Elizabeth M.;Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.
影响因子：
20.3
作者：
Gutierrez, Alejandro;Sanda, Takaomi;Look, A. Thomas
通讯作者：
Look, A. Thomas
影响因子：
20.3
作者：
Girardi T;Vicente C;Cools J;De Keersmaecker K
通讯作者：
De Keersmaecker K