FMS MUTATIONS IN PATIENTS FOLLOWING CYTOTOXIC THERAPY FOR LYMPHOMA
FMS MUTATIONS IN PATIENTS FOLLOWING CYTOTOXIC THERAPY FOR LYMPHOMA
复制标题
DOI：
10.1016/0145-2126(94)00128-w
复制
发表时间：
1995-05-01
影响因子：
2.7
通讯作者：
PADUA, RA
中科院分区：
文献类型：
--
作者：
BAKER, A;CACHIA, P;PADUA, RA
FMS原癌基因301和969密码子的点突变在骨髓发育不良症(MDS)和急性髓系白血病(AML)中都有报道。我们在此报告了有发生继发性MDS和AML风险的患者中此类突变的发生率。用突变特异性探针对70例淋巴瘤缓解期患者外周血DNA进行寡核苷酸(ONH)突变筛查。其中11例(15.7%)检测到969密码子突变。未检测到301密码子突变。用一种独立的技术(单核苷酸引物延伸分析，SNPE)证实了其中的5个突变，用单链构象多态分析(SSCP)在1例患者中检测到进一步的突变，在这些患者的62例淋巴瘤活检标本中没有检测到密码子969突变，或者从3例治疗前进行骨髓ONH检查的FMS突变患者中未检测到密码子969突变。ONH检测61例正常对照均未发现密码子301和969的突变。FMS基因969密码子的体细胞突变通常发生在淋巴瘤的细胞毒治疗后，它们的检测表明存在克隆性扩张的异常细胞群。
Point mutations at codons 301 and 969 of the FMS proto-oncogene have been reported in both myelodysplasia (MDS) and acute myeloid leukaemia (AML). We report here the incidence of such mutations in patients at risk of developing secondary MDS and AML. Peripheral blood DNA from 70 patients in remission from lymphoma was screened for mutations by oligonucleotide (ONH) using mutant specific probes. Codon 969 mutations were detected in 11 of the 70 (15.7%) cases. No codon 301 mutations were detected. Five of these mutations were confirmed using an independent technique (single nucleotide primer extension analysis, SNPE) and a further mutation was detected in a single patient using single-stranded conformational polymorphism analysis (SSCP), No codon 969 mutations were detected in 62 lymphoma biopsy specimens from these patients or from three patients with detectable FMS mutations where pre-therapy marrow was investigated by ONH. No mutations at either codons 301 or 969 were detected by ONH in 61 normal controls. Somatic mutations at codon 969 of the FMS gene occur commonly following cytotoxic therapy for lymphoma and their detection indicates the presence of a clonally expanded population of abnormal cells.