Wang Sheng-Mei, Zheng Hong-Jun, Tian Ying, Zhang Jian-Mei, Yao Jin-Hua
Department of Hematology, Qingyang Traditional Chinese Medicine Hospital, Qingyang 745000, Gansu Province, China.
Department of Clinical Laboratorial Examination, Qingyang People's Hospital, Qingyang 745000, Gansu Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Jun;28(3):797-801. doi: 10.19746/j.cnki.issn.1009-2137.2020.03.013.
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.
研究伴有29种融合基因和51种肿瘤基因的急性髓系白血病（AML）患者的基因突变情况。
采用二代测序（NGS）检测49种靶向基因。通过基于DNA的聚合酶链反应（PCR）和桑格测序检测FMS样酪氨酸激酶3（FLT3）内部串联重复（FLT3-ITD）、钙网蛋白（CALR）、核仁磷酸蛋白1（NPM1）和CCAAT增强子结合蛋白α（CEBPA）突变。采用多重巢式逆转录PCR检测29种融合基因。
121例患者的总基因突变率为91%（109/121）。平均每位患者鉴定出2.1个突变基因，在这121例患者中，≥3种突变共存很常见（34.7%）。最常发生突变的基因是NRAS（23.96%，n = 29），其次是NPM1（14.04%，n = 17）、CEBPA双突变（14.04%，n = 17）、KRAS（11.57%，n = 14）、FLT3-ITD（10.74%，n = 13）、集落刺激因子3受体（CSF3R）（10.74%，n = 13）、四氢叶酸还原酶2（TET2）（9.92%，n = 12）和异柠檬酸脱氢酶1（IDH1）（9.1%，n = 11）。总体而言，47例（37.3%）患者检测到融合基因，包括AML/ETO（n = 12）、核心结合因子β（CBFβ）/肌球蛋白重链11（MYH11）（n = 11）、早幼粒细胞白血病/维甲酸受体α（PML/RARa）（n = 12）、混合系白血病（MLL）重排相关突变MLL-X（n = 10）、 TLS/ERG（n = 1）和DEK/CAN（n = 1），频率依次降低。与核型异常患者相比，核型正常（NK）的AML患者在CEBPA、NPM1、TET2、 runt相关转录因子1（RUNX1）和IDH1基因有更多突变。核型异常患者的KRAS突变显著高于核型正常患者（P = 0.014）。TP53突变主要与复杂细胞遗传学相关（P = 0.199）。与NK-AML相比，KRAS突变在核心结合因子（CBF）急性髓系白血病（AML）和11q23/MLL重排白血病中更常见（分别为P = 0.006和0.003）。KIT突变在CBF-AML中占主导（P = 0.006）。在2例患者中检测到JAK2V617F突变，且与AML-ETO融合共存。
超过90%的患者至少观察到一种突变。平均每位患者鉴定出超过2个突变基因。一些基因突变与基因重排相关。
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