Migliazza A, Martinotti S, Chen W, Fusco C, Ye B H, Knowles D M, Offit K, Chaganti R S, Dalla-Favera R
Department of Pathology, Columbia University, New York, NY 10032, USA.
Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12520-4. doi: 10.1073/pnas.92.26.12520.
The BCL6 gene encodes a zinc-finger transcription factor and is altered by chromosomal arrangements in its 5' noncoding region in approximately 30% of diffuse large-cell lymphoma (DLCL). We report here that, in 22/30 (73%) DLCL and 7/15 (47%) follicular lymphoma (FL), but not in other tumor types, the BCL6 gene is also altered by multiple (1.4 x 10(-3) -1.6 x 10(-2) per bp), often biallelic, mutations clustering in its 5' noncoding region. These mutations are of somatic origin and are found in cases displaying either normal or rearranged BLC6 alleles indicating their independence from chromosomal rearrangements and linkage to immunoglobulin genes. These alterations identify a mechanism of genetic instability in malignant B cells and may have been selected during lymphomagenesis for their role in altering BCL6 expression.
BCL6基因编码一种锌指转录因子，在大约30%的弥漫性大细胞淋巴瘤（DLCL）中，其5'非编码区会因染色体排列而发生改变。我们在此报告，在22/30（73%）的DLCL和7/15（47%）的滤泡性淋巴瘤（FL）中，但在其他肿瘤类型中未发现，BCL6基因在其5'非编码区也会因多个（每碱基1.4×10⁻³ - 1.6×10⁻²）、通常为双等位基因的突变而改变，这些突变聚集在该区域。这些突变起源于体细胞，在显示正常或重排的BLC6等位基因的病例中均可发现，这表明它们与染色体重排无关，且与免疫球蛋白基因无连锁关系。这些改变确定了恶性B细胞中一种基因不稳定的机制，并且可能在淋巴瘤发生过程中因其在改变BCL6表达中的作用而被选择。
