白血病微卫星不稳定与靶基因移码突变的研究

Microsatellite instability and target gene frameshift mutations in leukemia

摘要:

探究微卫星不稳定（MSI）的急性淋巴细胞白血病（ALL）中1 和基因微卫星序列移码突变的情况。方法采用荧光片段聚合酶链反应（PCR）对ALL细胞株和临床样本行MSI检测。采用基因测序和荧光片段PCR 检测1 、基因微卫星序列的移码突变。结果ALL 细胞株MSI 阳性率为80.0%（4/5）；儿童ALL 患者骨髓样本MSI 阳性率为25.0%（3/12）；成人ALL 患者骨髓样本MSI 阳性率为20.0%（2/10）。Molt4 细胞株中1 基因微卫星序列存在移码突变c.22delC， 基因微卫星序列存在移码突变c.2560delA；CCRF-CEM 细胞株中1 基因微卫星序列存在移码突变c.22delC；ALL患者骨髓样本中1 和基因微卫星序列均未检测到上述移码突变。结论MSI诱导1 和基因微卫星序列移码突变可发生于ALL细胞株。

Abstract:

To investigate frameshift mutations of microsatellite sequence in and genes in acute lymphoblastic leukemia (ALL) with microsatellite instability (MSI). Methods Fluorescent frag-ment PCR was used for defining the microsatellite status of ALL cells both in cell lines and bone marrow samples. Sanger sequencing and fluorescent fragment PCR were used for the detection of frameshift mutations of microsatellite sequences in and genes in ALL cells with MSI both in cell lines and bone marrow samples. Results The incidence of MSI in the ALL cell line was 80.0% (4/5). The incidence of MSI in the child ALL cells was 25.0% (3/12). The incidence of MSI in the adult ALL was 20.0% (2/10).Frameshift mutations of c.22delC in gene and c.2560delA in gene were detected in Molt4 cell line. Frameshift mutation of c.22delC in gene was detected in CCRF-CEM cell line. None of the above frameshift mutations was detected in the ALL bone marrow samples. Conclusions MSI induced and gene frameshift mutations occur in the ALL cell lines.