Jia-Rui, Zhou, Fang, Wang, Ming, Liu, Yang, Zhang, Xue, Chen, Li-Li, Yuan, Yu, Zhang, Ming-Yu, Wang, Wei, Zhang, Jing, Zhang, Pan-Xiang, Cao, Jian-Cheng, Fang, Ming-Yue, Liu, Wei, Wang, and Hong-Xing, Liu
To study the correlation between tumor-associated somatic gene mutation and age in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia transformed from myelodysplastic syndrome (MDS/AML).A total of 111 patients primarily diagnosed as MDS or MDS/AML were selected. Bone marrow samples from patients were collected or bone marrow smears prepared at the initial diagnosis were used for detecting the somatic gene mutations of 58 genes related with hematologic tumors by high-throughput gene sequencing. And the correlation of gene mutations with the age of patients was analyzed.The positive rate of total gene mutation was 87.39% (97/111) in 111 patients, and 231 mutations in 28 different genes were detected in the patients with positive gene mutation. The patients of mutation-positive group were significantly older than that of the mutation-negative group (P<0.001). Among the mutation-positive patients, the mutation rate in the senile group (≥60 years) was 100% (14/14), followed by 89.04% (74/85) in the adult group (15-59 years) and 75% (9/12) in the children group (≤14 years). The average number of mutations in the children group, the adult group and the senile group were respectively 1.44, 2.47 and 2.5; the number of mutations in the adult group was greater than that in the children group (P<0.05).The most common mutations in the children group occurred in signal transduction gene (46.15%, 6/13); The most common mutations in both the adult group (22.40%, 41/183) and the senile group (34.29%, 12/35) occurred in epigenetic regulatory gene; the mutation rate of transcription factor gene in the senile group was higher than that in the children group (50.00% vs 8.33%) (P<0.05); the mutation rates of the splicing factor gene in the adult group and the senile group were higher than that in the children group (44.71% vs 8.33%) (P<0.05), (47.06% vs 8.33%) (P<0.05).The tumor-associated somatic gene mutations in patients with MDS and MDS/AML are significantly different between the different age groups, especially the children group and the adults group as well as the senile group, suggesting that the occurrence of MDS in children may involve genetic factors that are significantly different from those of adults and the senile.MDS及MDS/AML患者基因突变与年龄相关性分析.探讨骨髓增生异常综合征(myelodysplastic syndromes,MDS)及MDS转化为急性髓性白血病(acute myeloid leukemia,AML)患者血液肿瘤相关的体细胞基因突变与患者年龄的相关性.选取初诊MDS和MDS/AML患者共111例。采集患者骨髓样本或用初诊时留存的骨髓涂片,应用高通量基因测序方法检测血液肿瘤相关的58种基因的体细胞基因突变,分析基因突变与患者年龄的相关性.111例患者中总基因突变阳性率为87.39%(97/111),共检测到28种基因的231例次突变。基因突变阳性组患者年龄显著大于突变阴性组(P<0.001)。突变阳性的患者中,老年组(≥60岁)突变率最高,为100%(14/14),成人(15-59岁)组突变率为89.04%(74/85),儿童(≤14岁)组突变率为75%(9/12)。儿童组人均突变基因数目为1.44个,成人组2.47个,老年组2.5个;成人组突变个数显著大于儿童组(P=0.02)。儿童组信号转导基因突变最常见,突变率为46.15%(6/13),老年组和成人组表观遗传调节基因突变最常见,突变率分别为34.29%(12/35)和22.40%(41/183)。转录因子基因突变率在老年人组突变率高于儿童组(50.00% vs 8.33%)(P=0.036);剪接因子基因突变率在成人组和老年组中均高于儿童组(44.71% vs 8.33%)(P=0.024)、(47.06% vs 8.33%)(P=0.036).不同年龄组MDS及MDS/AML基因突变有所不同,尤其儿童组与成人组及老年组差异显著,提示儿童MDS的发生可能具有与成人和老年人MDS显著不同的遗传因素.