Primary mediastinal B-cell lymphoma: hypermutation of the BCL6 gene targets motifs different from those in diffuse large B-cell and follicular lymphomas.
Primary mediastinal B-cell lymphoma: hypermutation of the BCL6 gene targets motifs different from those in diffuse large B-cell and follicular lymphomas.
复制标题
原发性纵隔 B 细胞淋巴瘤：BCL6 基因的超突变靶向基序与弥漫性大 B 细胞和滤泡性淋巴瘤中的基序不同。
作者：
G. Malpeli;S. Barbi;P. Moore;M. Scardoni;M. Chilosi;A. Scarpa;F. Menestrina
背景和目标
BCL 6基因的体细胞超突变及其在淋巴瘤中的表达代表了B细胞通过生发中心转运的特异性标志物。因此，BCL 6的分析可能有助于阐明原发性纵隔B细胞淋巴瘤（PMBL）和其他非胸腺弥漫性大细胞淋巴瘤（DLCL）之间的关系。
设计和方法
通过定量逆转录聚合酶链反应（RT-PCR）和免疫组化分析了24例PMBL的BCL 6状态，包括第一内含子突变。我们还对PMBL（n=141）、DLCL（n=233）和滤泡性淋巴瘤（n=120）中报告的BCL 6突变进行了荟萃分析。
结果
13例PMBL（54%）显示BCL 6高突变。所有病例均有bcl 6 mRNA和免疫组化表达。荟萃分析表明，在PMBL中BCL 6的优先改变的序列基序是TA（p=0.002）和AT（p=0.0008）二核苷酸和达特三核苷酸（p=0.001）。GC和RGYW/WRCY基序在DLCL和FL中是靶点，但在PMBL中不是。此外，跨越核苷酸150-270的DNA片段仅在PMBL中高度靶向。
解释和结论
bcl-6蛋白的一致表达和高突变的发生表明PMBL可能为生发中心起源。PMBL中BCL 6的超突变位点和突变谱与FL和DLCL中发现的不同，这一事实可能表明这些肿瘤类型之间转化细胞的成熟阻滞不同，并且在肿瘤转化之前存在特征性突变模式。因此，我们的研究结果加强了PMBL起源于已经定义的B细胞亚群的假设，这与导致DLCL或FL的B细胞亚群不同。
BACKGROUND AND OBJECTIVES
Somatic hypermutation of the BCL6 gene and its expression in lymphoma represent specific markers for B-cell transit through the germinal center. Thus, analysis of BCL6 may aid in clarifying the relationship between primary mediastinal B-cell lymphoma (PMBL) and other non-thymic diffuse large cell lymphomas (DLCL).
DESIGN AND METHODS
Twenty-four PMBL were analyzed for BCL6 status, including first intron mutations, by quantitative reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. We also performed a meta-analysis of reported BCL6 mutations in PMBL (n=141), DLCL (n=233), and follicular lymphoma (n=120).
RESULTS
Thirteen PMBL (54%) showed hypermutation of BCL6. All cases showed bcl6 mRNA and immunohistochemical expression. Meta-analysis demonstrated that the preferentially altered sequence motifs of BCL6 in PMBL were TA (p=0.002) and AT (p=0.0008) dinucleotides and TAT trinucleotides (p=0.001). GC and RGYW/WRCY motifs were a target in DLCL and FL but not in PMBL. Moreover, the DNA stretch spanning nucleotides 150-270 was highly targeted only in PMBL.
INTERPRETATION AND CONCLUSIONS
The consistent expression of bcl6 protein and occurrence of hypermutation indicate that PMBL should be considered of germinal center origin. The fact that the hypermutation sites and mutational spectrum of BCL6 in PMBL differ from those found in FL and DLCL might suggest that the maturation block of the transforming cells differs among these tumor types, and that the characteristic mutational pattern is present before neoplastic transformation. Thus, our findings strengthen the hypothesis that PMBL originate from an already defined sub-population of B-cells, which are different from those leading to either DLCL or FL.
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DOI：
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DOI：
10.1016/s0002-9440(10)64969-3
发表时间：
2000
期刊：
The American journal of pathology
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