骨髓增生异常综合征患者中TET2基因突变的检测与临床意义

Clinical significance of TET2 mutation in patients with myelodysplastic syndromes

目的:探讨TET2基因在骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者中突变发生率及对预后的影响。方法:随机选取95例初诊MDS患者,采用R显带技术进行常规核型分析(CC),PCR技术及直接测序法检测基因序列;分析该95例初诊MDS患者的临床和实验室特征。结果:95例初诊MDS患者中11例发生TET2基因突变,突变率为11.6%,其中6例发生错义突变,1例2次错义突变,2例无义突变,2例同义突变,5例TET2基因突变位点位于3号外显子上。95例MDS患者中位随访时间为13个月(2～73个月),伴有TET2基因突变的MDS患者中位生存期短于未发生该基因突变者且生存率较低(9个月vs 15个月,P<0.05)。结论:TET2基因突变是一种新型分子学异常,伴有该基因突变的MDS患者预后较差。

Objective： To investigate the frequency and the influence to prognosis of TET2 mutation in patients with myelodysplastic syndromes （MDS）. Methods： Randomly, we chose 95 primary MDS patients. Genomic DNA from mononuclear cells in bone marrow was extracted by DNA kits and amplified through allele-specific polymerase chain reaction （PCR）. TET2 gene sequences were detected directly. The clinical and laboratory features of the 95 primary MDS patients were analyzed. Results： In this study, TET2 mutation was found in 11 out of 95 patients with an incidence of 11.6%, containing 6 cases with missense mutation, 2 with nonsense mutation, 2 with same sense mutation, as well as 1 with both mutations, respectively. Amongst which, 5 cases were mutated in exon 3. Totally, during a median follow-up of 13 months （2 -73 months）, 9 primary MDS patients were found TET2 mutated while 51 patients were not. Compared to the unmutated group, the TET2 mutated group had shorter lives with a median survival of 9 months vs 15 months （P 〈 0. 05 ）. Conclusion： TET2 mutation is a molecular abnormality commonly seen in MDS, with which patients might have a poor prognosis.