MUC1 is activated in a B-cell lymphoma by the t(1;14)(q21;q32) translocation and is rearranged and amplified in B-cell lymphoma subsets.
MUC1 is activated in a B-cell lymphoma by the t(1;14)(q21;q32) translocation and is rearranged and amplified in B-cell lymphoma subsets.
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MUC1 在 B 细胞淋巴瘤中通过 t(1;14)(q21;q32) 易位被激活，并在 B 细胞淋巴瘤亚群中重排和扩增。
DOI：
10.1182/blood.v95.8.2666.008k02_2666_2671
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发表时间：
2000
期刊：
影响因子：
20.3
通讯作者：
R. Chaganti
中科院分区：
文献类型：
--
作者：
V. Dyomin;N. Palanisamy;Kenneth O. Lloyd;Katerina Dyomina;S. Jhanwar;J. Houldsworth;R. Chaganti
在淋巴、髓、上皮和肉瘤病变中，1q21是染色体易位最常见的位点之一。在非霍奇金淋巴瘤（NHL）中，影响该染色体位点的易位和重复经常（但不是唯一）与原发性异常相关，如t(14;18)（q32;q21）和t(8;14)（q24;q32）易位，提示1q21重排在肿瘤进展中的作用。我们在此报告了一例伴有t(1;14)（q21;q32）易位的结外腹水b细胞淋巴瘤断点的特征和克隆。利用荧光原位杂交和Southern blot分析确定了der(1)和der（14）染色体上的断点，并利用IGHG （Cgamma）探针进行了克隆。易位将有效重排等位基因的IGHG4开关（Sgamma4）序列连接到MUC1下游的1号染色体序列，使MUC1转录单元保持完整。MUC1在肿瘤中的mRNA和蛋白水平明显过表达，相对于缺乏1q21重排的淋巴瘤细胞系。据推测，MUC1的转录受到保留在同一染色体上的IGHA (Calpha) 3'增强子元件的异常调节。通过Southern blot分析筛选一组b细胞淋巴瘤，发现一个亚群具有3' MUC1断点，另一个亚群具有MUC1低水平扩增。muc1粘蛋白先前已被证明在人类上皮癌中经常过表达，并与肿瘤进展和不良临床结果相关。因此，MUC1通过染色体易位、重排和扩增激活，首次在NHL中被发现，这与其在肿瘤发生中的作用是一致的。(血。2000;95:2666 - 2671)
The band 1q21 is among the most common sites affected by chromosomal translocations in lymphoid, myeloid, epithelial, and sarcomatous lesions. In non-Hodgkin's lymphoma (NHL), translocations and duplications affecting this chromosomal site are frequently, but not exclusively, seen in association with primary abnormalities such as the t(14;18)(q32;q21) and t(8;14)(q24;q32) translocations, suggesting a role for 1q21 rearrangements in tumor progression. We report here the characterization and cloning of breakpoints in a case of extranodal ascitic B-cell lymphoma with a t(1;14)(q21;q32) translocation. The breakpoints on the der(1) and der(14) chromosomes were mapped by fluorescence in situ hybridization and Southern blot analysis and cloned using an IGHG (Cgamma) probe. The translocation linked the IGHG4 switch (Sgamma4) sequences of the productively rearranged allele to chromosome 1 sequences downstream of MUC1, leaving the MUC1 transcriptional unit intact. MUC1 was markedly overexpressed in the tumor at the mRNA and protein levels relative to lymphoma cell lines lacking a 1q21 rearrangement. Presumably, MUC1 transcription is aberrantly regulated by the IGHA (Calpha) 3' enhancer element retained on the same chromosome. Screening of a panel of B-cell lymphomas by Southern blot analysis identified a subset with a 3' MUC1 breakpoint and another with low-level amplification of MUC1. MUC-1 mucin has previously been shown to be frequently overexpressed in human epithelial cancers and to be associated with tumor progression and poor clinical outcome. Thus, MUC1 activation by chromosomal translocation, rearrangement, and amplification, identified here for the first time in NHL, is consistent with its suggested role in tumorigenesis. (Blood. 2000;95:2666-2671)