An integrated genomic and expression analysis of 7q deletion in splenic marginal zone lymphoma.
An integrated genomic and expression analysis of 7q deletion in splenic marginal zone lymphoma.
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DOI：
10.1371/journal.pone.0044997
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Du MQ
中科院分区：
文献类型：
--
作者：
Watkins AJ;Hamoudi RA;Zeng N;Yan Q;Huang Y;Liu H;Zhang J;Braggio E;Fonseca R;de Leval L;Isaacson PG;Wotherspoon A;McPhail ED;Dogan A;Du MQ
脾边缘带淋巴瘤(SMZL)是一种以7q32缺失为特征的惰性B细胞淋巴增生性疾病，但该缺失的靶基因尚不清楚。为了阐明这个缺失的遗传靶点，我们对遗传学、表观遗传学、转录和微基因组数据进行了综合分析。56例SMZL的高分辨阵列比较基因组杂交显示在7q32有一个最小缺失区域(2.8Mb)，但没有证据表明该区域存在隐匿的纯合子缺失或反复出现的断裂点。综合转录分析证实，在缺失的SMZL病例中，该区域的一些基因显著表达不足，其中一些基因表现出高度甲基化。此外，在缺失的病例中，该区域的8个miRNA簇显示低表达，其中3个(miR-182/96/183)在SMZL中的表达也显著低于其他淋巴瘤(P<；0.05)。对这些miRNA和一个强有力的候选基因IRF5进行基因组测序，没有发现SMZL有任何体细胞突变的证据。这些观察结果为进一步鉴定7q缺失提供了有价值的指导。
Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion, but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8 Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrated transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P<0.05) in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL. These observations provide valuable guidance for further characterisation of 7q deletion.
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