Li Meng-Ju, Yang Yung-Li, Lee Ni-Chung, Jou Shiann-Tarng, Lu Meng-Yao, Chang Hsiu-Hao, Lin Kai-Hsin, Peng Ching-Tien, Lin Dong-Tsamn
Department of Pediatrics, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
Department of Laboratory Medicine, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan.
J Formos Med Assoc. 2016 Sep;115(9):801-6. doi: 10.1016/j.jfma.2015.08.002. Epub 2015 Sep 26.
BACKGROUND/PURPOSE: Mutations in the tet oncogene family member 2 gene (TET2) are frequently found in adult patients with acute myeloid leukemia (AML). Reports of TET2 mutations in children are limited. We assessed the prevalence of TET2 mutations in Taiwanese children with AML and analyzed their prognosis.
Between 1997 and 2010, a total of 69 consecutive children with AML were enrolled at the National Taiwan University Hospital. The analysis for TET2 mutations was performed using direct sequencing. Clinical characteristics and overall survival (OS) were compared between patients with and without TET2 alterations.
Intronic and missense mutations were identified. No nonsense or frameshift mutations were observed. Two putative disease-causing missense mutations (S609C and A1865G) were identified in one patient. We estimated the prevalence of TET2 mutations in the current patient population to be 1.4%. The most common polymorphism was I1762V (45%), followed by V218M (12%), P29R (6%), and F868L (6%). Patients with polymorphism I1762V had an increased 10-year survival rate compared with patients without I1762V (48.4% vs. 25.7%, p = 0.049) by Chi-square test; OS was not different when examined using the Kaplan-Meier method (p = 0.104).
The prevalence of TET2 mutations in children with AML compared with adults with AML was lower and less complex. Patient prognosis associated with TET2 mutations in children requires further investigation.
背景/目的：成人急性髓系白血病（AML）患者中经常发现tet癌基因家族成员2基因（TET2）突变。儿童TET2突变的报道有限。我们评估了台湾儿童AML患者中TET2突变的发生率，并分析了其预后。
1997年至2010年期间，国立台湾大学医院共纳入69例连续的儿童AML患者。采用直接测序法进行TET2突变分析。比较有和没有TET2改变的患者的临床特征和总生存期（OS）。
鉴定出内含子和错义突变。未观察到无义或移码突变。在一名患者中鉴定出两个推定的致病错义突变（S609C和A1865G）。我们估计当前患者群体中TET2突变的发生率为1.4%。最常见的多态性是I1762V（45%），其次是V218M（12%）、P29R（6%）和F868L（6%）。通过卡方检验，I1762V多态性患者的10年生存率高于无I1762V的患者（48.4%对25.7%，p = 0.049）；使用Kaplan-Meier方法检验时，OS无差异（p = 0.104）。
与成人AML患者相比，儿童AML患者中TET2突变的发生率较低且不那么复杂。儿童TET2突变相关的患者预后需要进一步研究。
