Homozygous deletion mapping in myeloma samples identifies genes and an expression signature relevant to pathogenesis and outcome.
Homozygous deletion mapping in myeloma samples identifies genes and an expression signature relevant to pathogenesis and outcome.
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DOI：
10.1158/1078-0432.ccr-09-2831
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发表时间：
2010-03-15
期刊：
影响因子：
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通讯作者：
Morgan GJ
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文献类型：
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作者：
Dickens NJ;Walker BA;Leone PE;Johnson DC;Brito JL;Zeisig A;Jenner MW;Boyd KD;Gonzalez D;Gregory WM;Ross FM;Davies FE;Morgan GJ
骨髓瘤是浆细胞的克隆性恶性肿瘤。预后不良的风险目前由临床和细胞遗传学特征确定。然而，这些指标并不能反映所有的预后信息。基因表达分析可以用来识别预后不良的患者，结合DNA水平变化的信息可以改善这一点。使用基于SNP的基因定位结合全球基因表达分析，我们已经确定了与骨髓瘤发病机制和预后相关的基因和网络中的纯合子缺失。我们鉴定出170个基因存在纯合缺失和相应的表达缺失。“细胞死亡”网络中的缺失比例过高，存在这些缺失的病例损害了总体存活率。通过对这些事件的进一步分析，我们在258名患者中产生了一个与较短生存期相关的基于表达的签名，并在两个独立小组总计800名患者的数据中证实了这一签名。我们定义了97个细胞死亡基因的基因表达特征，反映了预后，在两个独立的数据集中得到了证实。我们从97个基因的签名中开发了一个简单的6个基因表达签名，可以用来在临床环境中识别预后不良的骨髓瘤。这一签名可以为未来旨在改善预后不良的骨髓瘤结果的试验奠定基础。
Myeloma is a clonal malignancy of plasma cells. Poor prognosis risk is currently identified by clinical and cytogenetic features. However, these indicators do not capture all prognostic information. Gene expression analysis can be used to identify poor prognosis patients and this can be improved by combination with information about DNA level changes. Using SNP-based gene mapping in combination with global gene expression analysis we have identified homozygous deletions in genes and networks that are relevant to myeloma pathogenesis and outcome. We identified 170 genes with homozygous deletions and corresponding loss of expression. Deletion within the “Cell Death” network was over-represented and cases with these deletions have impaired overall survival. From further analysis of these events, we have generated an expression-based signature associated with shorter survival in 258 patients and confirmed this signature in data from 2 independent groups totalling 800 patients. We defined a gene expression signature of 97 cell death genes that reflects prognosis confirmed this in two independent data sets. We developed a simple 6-gene expression signature from the 97-gene signature that can be used to identify poor prognosis myeloma in the clinical environment. The signature can form the basis of future trials aimed at improving the outcome of poor prognosis myeloma.