Chaganti S R, Chen W, Parsa N, Offit K, Louie D C, Dalla-Favera R, Chaganti R S
Laboratory of Cancer Genetics, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Genes Chromosomes Cancer. 1998 Dec;23(4):323-7.
Chromosomal band 3q27 exhibits recurring and nonrecurring translocations and other rearrangements in approximately 8% of B-cell non-Hodgkin lymphomas (NHL) belonging to low-grade as well as diffuse aggressive histologies. The BCL6 gene, which encodes a zinc-finger transcription repressor protein and which maps to chromosomal band 3q27, is deregulated in t(3;14)(q27;q32) and other translocations by substitution of its transcription regulatory sequences by those of genes on the partner chromosomes. To delineate the cytogenetics and investigate the nature and consequence of BCL6 involvement in the spectrum of 3q27 aberrations seen in NHL, we analyzed a panel of 53 NHL tumors with 3q27 aberrations for BCL6 gene rearrangements and a subset of 32 of these for mutations. We identified four new recurring translocations involving 3q27, in addition to the previously recognized t(3;14)(q27;q32) and its variant, t(3;22)(q27;q11). Histologically, the 3q27 breaks were represented by 4% mantle cell lymphomas, 38% follicular center cell lymphomas, and 58% diffuse large B-cell lymphomas. Approximately 50% of the tumors exhibited BCL6 rearrangements, whereas 87.5% showed mutations in the 5' noncoding region which contains the transcription regulatory sequences. These results demonstrate that a substantial proportion of cytogenetically detected 3q27 breaks in NHLs do not represent BCL6-associated translocations. They also suggest alternate breakpoints which may lead to BCL6 deregulation, or involvement of other genes in 3q27 translocations. The frequent BCL6 mutation in these tumors is consistent with our previous observation of hypermutation of the 5' noncoding region of the gene in lymphomas arising in the germinal-center B-cells.
染色体带3q27在大约8%的低级别以及弥漫性侵袭性组织学类型的B细胞非霍奇金淋巴瘤（NHL）中出现反复和非反复的易位及其他重排。编码锌指转录抑制蛋白且定位于染色体带3q27的BCL6基因，在t(3;14)(q27;q32)及其他易位中因转录调控序列被伙伴染色体上的基因序列取代而失调。为了描绘细胞遗传学特征并研究BCL6参与NHL中所见3q27畸变谱的性质和后果，我们分析了一组53例有3q27畸变的NHL肿瘤的BCL6基因重排情况，并对其中32例的一个子集进行了突变分析。除了先前确认的t(3;14)(q27;q32)及其变体t(3;22)(q27;q11)外，我们还鉴定出了四种涉及3q27的新的反复易位。组织学上，3q27断裂在4%的套细胞淋巴瘤、38%的滤泡中心细胞淋巴瘤和58%的弥漫性大B细胞淋巴瘤中出现。大约50%的肿瘤表现出BCL6重排，而87.5%在包含转录调控序列的5'非编码区显示出突变。这些结果表明，在细胞遗传学检测到的NHL中3q27断裂的很大一部分并不代表与BCL6相关的易位。它们还提示了可能导致BCL6失调的替代断点，或其他基因参与3q27易位。这些肿瘤中频繁的BCL6突变与我们先前在生发中心B细胞来源的淋巴瘤中观察到的该基因5'非编码区的高突变一致。
