Jardin F, Ruminy P, Parmentier F, Picquenot J M, Courel M N, Bertrand P, Buchonnet G, Tilly H, Bastard C
Department of Clinical Hematology, Centre Henri Becquerel, Rouen, France.
Leukemia. 2005 Oct;19(10):1824-30. doi: 10.1038/sj.leu.2403915.
Genetic modifications of the BCL6 gene in lymphoma include translocations, deletions, and somatic mutations (SM) of the 5' noncoding region. Three single-nucleotide polymorphisms (SNPs) of the major mutation cluster region (MMC) have been reported, including two substitutions (397G/C, 502G/A) and one deletion (520DeltaT). Clinical and biological relevance of these SNPs are unknown. Based on a case-control study, BCL6 SNPs frequencies were assessed in 97 t(14;18) follicular lymphomas (FL) and in 54 lymphomas with 3q27 rearrangement. Allele frequencies were similar in the FL and controls groups. The 397 G/C genotype was correlated to a higher-grade transformation risk (P=0.02). SM were observed in 39.1% of FL and were characterized by a clustering distribution (hot spots spanning position 420-435, 106-127, and 590-600). No correlation between genotypes or acquired mutational status and BCL6 expression was demonstrated. However, gel mobility-shift assays, using SNPs containing probes show results representative for protein/DNA complexes. This study demonstrates that the first BCL6 intron is a highly variable region as a consequence of both SNP and SM, which may contribute to biology and outcome of FL.
淋巴瘤中BCL6基因的遗传修饰包括5'非编码区的易位、缺失和体细胞突变（SM）。已报道主要突变簇区域（MMC）的三个单核苷酸多态性（SNP），包括两个替换（397G/C、502G/A）和一个缺失（520DeltaT）。这些SNP的临床和生物学相关性尚不清楚。基于一项病例对照研究，在97例t(14;18)滤泡性淋巴瘤（FL）和54例3q27重排的淋巴瘤中评估了BCL6 SNP频率。FL组和对照组的等位基因频率相似。397 G/C基因型与更高等级的转化风险相关（P=0.02）。在39.1%的FL中观察到SM，其特征为聚集分布（热点跨越位置420-435、106-127和590-600）。未证明基因型或获得性突变状态与BCL6表达之间存在相关性。然而，使用含SNP的探针进行凝胶迁移率变动分析显示了蛋白质/DNA复合物的代表性结果。本研究表明，由于SNP和SM，BCL6第一个内含子是一个高度可变的区域，这可能有助于FL的生物学特性和预后。
