TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma

TNFAIP3 is the target gene of chromosome band 6q23.3-q24.1 loss in ocular adnexal marginal zone B cell lymphoma
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DOI:
10.1002/gcc.20499
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发表时间:
2008-01-01
影响因子:
3.7
通讯作者:
Seto, Masao
Seto, Masao
中科院分区:
医学2区
文献类型:
--
作者:
Honma, Keiichiro;Tsuzuki, Shinobu;Seto, Masao

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结外边缘区B细胞淋巴瘤的基因组畸变因其解剖学起源而异。这种两极分化反映了不同基因参与边缘区B细胞淋巴瘤的发生。我们先前通过全基因组阵列比较基因组杂交(CGH)证明了眼附属器边缘区B细胞淋巴瘤的基因组图谱不同于肺或结边缘区B细胞淋巴瘤。新的发现是在眼附属器边缘区B细胞淋巴瘤中染色体带6q23.3-q24.1的2.9-M B区域的复发性缺失,包括纯合缺失。为了更详细地检查6q23.3-24.1的缺失,我们使用重叠群细菌人工染色体(BAC)阵列CGH,包含覆盖2.9-Mb区域的24个BAC克隆,以分析9例6q23.3-q24.1缺失。我们将最小共同区域的长度缩小到586 kb,具有两个基因和四个表达序列标签(EST)。所有这些基因和ESTs进行RT-PCR和实时定量RT-PCR。仅发现TNFAIP 3的基因组丢失与表达水平相关,表明TNFAIP 3是眼附属器边缘区B细胞淋巴瘤中6 q缺失的靶基因。TNFAIP 3是NF-kB信号传导的抑制剂,因此该基因的缺失可能在淋巴瘤发生中起重要作用,并表明TNFAIP 3可能在眼附属器边缘区B细胞淋巴瘤中作为肿瘤抑制基因。本文包含可在http://www.interscience上获得的补充材料。wiley.com/jpages/1045-2257/suppmat. (c)2007 Wiley-Liss,Inc.
The genomic aberrations in extra nodal marginal zone B cell lymphoma vary according to their anatomical origin. This polarization is a reflection of the participation of different genes in the lymphomagenesis of marginal zone B cell lymphoma. We previously demonstrated by means of genome-wide array comparative genomic hybridization (CGH) that the genomic profile of ocular adnexal marginal zone B cell lymphoma is distinct from that of pulmonary or nodal marginal zone B cell lymphoma. The novel finding was a recurrent deletion of a 2.9-Mb region at chromosome band 6q23.3-q24.1, including homozygous loss, in ocular adnexal marginal zone B cell lymphoma. For a more detailed examination of the deletions of 6q23.3-24.1, we used contig bacterial artificial chromosome (BAC) array CGH, containing 24 BAC clones covering the 2.9-Mb region, to analyze nine cases with 6q23.3-q24.1 loss. We narrowed the minimal common region down to a length of 586 kb with two genes and four expressed sequence tags (ESTs). All of these genes and ESTs were subjected to RT-PCR and real-time quantitative RT-PCR. Correlation between genomic loss and expression level was found only for TNFAIP3, demonstrating that TNFAIP3 is a target gene of 6q deletion in ocular adnexal marginal zone B cell lymphoma. TNFAIP3 is an inhibitor of NF-kB signaling so that loss of this gene may play an important role in lymphomagenesis and suggests that TNFAIP3 may act as a tumor suppressor gene in ocular adnexal marginal zone B cell lymphoma. This article contains Supplementary Material available at http://www.interscience. wiley.com/jpages/1045-2257/suppmat. (c) 2007 Wiley-Liss, Inc.