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多发性骨髓瘤患者IgH-MMSET基因的检测及其意义 被引量:5

Detection of IgH-MMSET fusion gene in multiple myeloma patients and its significance
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摘要 目的 检测多发性骨髓瘤 (MM)患者由于t(4;14 )所形成的IgH MMSET融合基因 ,探讨其在MM中的临床意义。方法 采用RT PCR法在 2 5例MM患者骨髓标本和MM细胞系NCI H92 9中检测IgH MMSET融合基因 ,并且通过巢式PCR法提高反应的灵敏度。PCR产物纯化后克隆到pGEM T载体 ,并用引物M13Forward测序。将PCR产物的序列与GenBank进行对照 ,进一步证实发生易位的基因。结果 作为阳性对照的MM细胞系NCI H92 9扩增出一明显条带 ,长度为 4 38bp ,经测序后证实为IgH基因与MMSET基因的融合产物。 14号染色体及 4号染色体上的断裂点分别位于IgH基因的Cμ区及MMSET基因的第 3内含子中。 2 5例MM患者的骨髓标本扩增后有 3例 (12 .0 % )呈现阳性 ,经分别测序后证实为IgH MMSET融合基因 ,扩增产物的长度分别为 2 37bp、2 39bp和 2 39bp ,三者第 4染色体的断裂方式均与NCI H92 9相同 ,其中 1例缺失了MMSET基因的第 4外显子的第 74位碱基 (A)和第 75位碱基 (T)。结论 MM患者IgH MMSET融合基因是由于t(4;14 )所形成 ,其发生率为 12 .0 %。IgH MMSET融合基因的出现可能是MM患者预后不良的指标之一。 Objective To detect the IgH-MMSET fusion gene resulted from t (4;14) translocation in multiple myeloma and illuminate its significance. Methods IgH-MMSET fusion gene was detected in bone marrow specimens of 25 multiple myeloma (MM) patients and MM cell line NCI-H929 using reverse-transcription PCR (RT-PCR) assay followed by nested PCR to increase the sensitivity.The purified PCR products were cloned into pGEM-T vector and then sequenced using M13 forward primers. The fragment sequences were compared with that in GenBank to find matched sequences. Results Only a 438 base pair long fragment was obtained after RT-PCR assay and was confirmed by sequencing to be a fusion gene product of IgH gene and MMSET gene in MM cell line NCI-H929. The breakpoints were located within the Cμ region of IgH gene on chromosome 14 and intron 3 of MMSET gene on chromosome 4. IgH-MMSET hybrid transcripts were detected in 3 of 25 MM patients through nested PCR assay. The amplified fragments of the 3 patients were 237 base pairs (bp), 239 bp and 239 bp in length, respectively. The breakpoints on chromosome 4 were identical to that of NCI-H929 cell. Conclusions The formation of IgH-MMSET fusion gene is resulted from t(4;14) translocation in MM. The incidence rate is 12.0%. The presence of IgH-MMSET fusion gene may predict poor prognosis.
出处 《中华血液学杂志》 CAS CSCD 北大核心 2003年第10期515-518,共4页 Chinese Journal of Hematology
基金 教育部高校骨干教师基金 上海市卫生局"百人计划"课题 (98BR0 3 2 ) 全军"九五"课题 (98M0 82 )资助项目
关键词 多发性骨髓瘤 IgH-MMSET 基因 检测 RT-PER法 Multiple myeloma Gene fusion,IgH-MMSET Translocation(Genetics)
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