| Popis: |
To investigate the gene mutation occurved in AML patients with 29 kinds of fusion genes and 51 kinds of tumor gene.Next-generation sequencing (NGS) was used to detected the 49 kinds of targeted gene. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutation were detected by DNA-based PCR and Sanger sequencing. Twenty-nine kinds of fusion genes were dected by multiplex nested RT-PCR.The total gene mutation rate was 91% (109/121) in all the 121 patients. On average, 2.1 mutated genes per patient were identified, among these 121 patients, coexistence of ≥ 3 mutations was frequent (34.7%). The most commonly mutated genes were NRAS (23.96%, n=29), followed by NPM1 (14.04%, n=17), CEBPA double mutations (14.04%, n=17), KRAS (11.57%, n=14)，FLT3-ITD (10.74%, n=13), CSF3R (10.74%, n=13), TET2 (9.92%, n=12) and IDH1 (9.1%, n=11). Overall, fusion genes were detected in 47 (37.3%) patients, including AML/ETO (n=12), CBFβ/MYH11 (n=11), PML/RARa (n=12), MLL rearranagement realated mutation MLL-X (n=10). TLS/ERG (n=1) and DEK/CAN (n=1) in an order of decreasing frequency. Patients with normal karyotype (NK)- AML exhibited more mutations in CEBPA, NPM1, TET2, RUNX1 and IDH1, comparing with abnormal karyotype patients. KRAS mutation in abnormal kayotype patients was significantly higher than that in normal kayotype patients (P=0.014). TP53 mutations were predominantly associated with complex cytogenetics (P=0.199). KRAS mutations were more frequent in core binding factor (CBF) acute myeloid leukemia (AML) and 11q23/MLL rearrangement leukemia, compared with NK-AML (P=0.006 and 0.003, respectively). KIT mutations predominated in CBF-AML (P=0.006). JAK2V617F mutations were detected in two patients and co-occurred with AML-ETO fusions.At least one mutation is observed in more than 90% patients. On average, more than 2 mutated genes per patient are identified. Some gene mutations are associated with gene rearrangement.121例急性髓系白血病患者基因突变谱的分析.研究急性髓系白血病（AML）患者29种融合基因及51种肿瘤基因突变的发生情况.采用第二代DNA测序技术检测49种靶基因；采用DNA-PCR检测FLT3-ITD、NPM1基因12号外显子、CALR基因9号外显子及CEBPA的TAD、BZIP 2个功能区的突变发生情况；采用多重PCR法检测29种白血病融合基因.121例患者中，基因突变总发生率为90.1%（109/121），每例患者平均发生2.1个基因突变，34.7%的患者同时携带≥3个基因突变。突变检出率最高的基因为NRAS（23.96%，n=29），其他基因依次为：NPM1（14.04%，n=17）、CEBPA双突变（14.04%，n=17）、KRAS（11.57%，n=14）、FLT3-ITD（10.74%，n=13）、CSF3R（10.74%，n=13）、TET2（9.92%，n=12）和IDH1（9.1%，n=11）。共47例患者检出融合基因，包括AML/ETO 12例，CBFβ/MYH11 11例，PML/RARa 12例，涉及MLL重排的MLL-X融合基因10例，TLS/ERG 1例及DEK/CAN 1例。 CEBPA、NPM1、TET2、RUNX1及IDH1突变在正常核型中的检出率均高于异常核型，差异有统计学意义；KRAS突变在异常核型中的发生率高于正常核型，差异显著（P=0.014）。复杂核型患者的TP53突变检出率明显高于正常核型及其他异常核型（P=0.199）。KRAS突变在核心结合因子白血病及伴有11q23/MLL重排的M5患者中的阳性率均高于正常核型（P=0.006，P=0.003）。KIT基因突变主要见于核心结合因子白血病，两者有相关性（P=0.006）。共检测到2例JAK2V617F突变，均与t (8; 21)/AML1/ETO伴随出现.大于90%的AML患者至少携带1个基因突变，每例患者平均发生2个以上白血病常见致病基因突变，部分基因突变与基因重排有一定相关性. |
