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目的:探究CEBPA基因双端突变与单端突变2种突变模式的伴随附加基因突变分布差异,并讨论其与患者预后间的潜在相关性。方法:对152例正常核型初发急性髓细胞白血病(acute myeloid leukemia,AML)患者中,25个AML驱动基因的热点区域进行二代深度测序,并结合一代测序验证检测突变位点,利用卡方检验或Fisher检验对CEBPA基因双端突变和单端突变所伴随的附加基因突变情况进行统计分析。结果:152例正常核型的初发AML患者中,CEBPA基因双端突变43例(28.29%),CEBPA基因单端突变13例(8.55%)。携带CEBPA基因单端突变患者伴3个以上附加基因突变百分比高于CEBPA基因双端突变(P=0.043)。在携带CEBPA基因双端突变患者中,未发现伴NPM1基因突变,而在13例CEBPA基因单端突变患者中,有6例伴NPM1突变(P<0.001)。附加基因突变分布分析中,CEBPA基因单端突变患者伴更多的DNA甲基化修饰基因突变(DNMT3A、TET2、IDH1、IDH2)(P=0.046);CEBPA基因单端突变伴随更多的叠加高危组基因突变(DNMT3A、FLT3-ITD、TP53)。结论 :CEBPA单端突变比双端突变患者伴随更多的预示不良预后的附加突变,可能与CEBPA基因双端突变及单端突变2种突变模式的预后差异相关。
OBJECTIVE: To explore the distribution of additional mutations associated with two mutations in the double-terminal and single-terminal mutations of CEBPA gene and to discuss the potential correlation between CEBPA mutations and the prognosis of patients. Methods: A total of 152 AML patients with acute myeloid leukemia (AML) were genotyped by deep sequencing of 25 AML-driven hotspots, followed by the detection of a single nucleotide polymorphism Square test or Fisher’s test for the CEBPA gene double-ended mutations and single-ended mutations associated with additional gene mutations were statistically analyzed. Results: There were 43 patients (28.29%) with CEBPA gene mutation and 13 (8.55%) patients with CEBPA gene mutation in 152 AML patients with normal karyotype. The percentage of more than 3 additional genes with single-terminal mutations in CEBPA was higher than that in CEBPA (P = 0.043). No NPM1 gene mutation was found in patients with double-stranded mutations of the CEBPA gene, whereas 6 of the 13 patients with single-terminal mutations in the CEBPA gene had NPM1 mutations (P <0.001). In additional gene mutation distribution analysis, more DNA methylation-modified mutations (DNMT3A, TET2, IDH1, IDH2) were associated with more mutations in the CEBPA gene (P = 0.046) Group of gene mutations (DNMT3A, FLT3-ITD, TP53). CONCLUSIONS: Additional mutations with more CEBPA mutations than those with double-stranded mutations in predicting poor prognosis may be related to the differences in the prognosis of the two mutations of the CEBPA gene and the single-terminal mutation.