Section of Haemato-Oncology, The Institute of Cancer Research, London, United Kingdom.
Clin Cancer Res. 2010 Mar 15;16(6):1856-64. doi: 10.1158/1078-0432.CCR-09-2831. Epub 2010 Mar 9.
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 single nucleotide polymorphism-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 overrepresented and cases with these deletions had 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 two independent groups totaling 800 patients. We defined a gene expression signature of 97 cell death genes that reflects prognosis and 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. This signature could form the basis of future trials aimed at improving the outcome of poor-prognosis myeloma.
骨髓瘤是一种浆细胞的克隆性恶性肿瘤。目前通过临床和细胞遗传学特征来确定预后不良的风险。然而，这些指标并未捕捉到所有的预后信息。基因表达分析可用于识别预后不良的患者，并且通过结合有关 DNA 水平变化的信息可以改善这一点。
我们使用基于单核苷酸多态性的基因图谱结合全基因表达分析，鉴定了与骨髓瘤发病机制和结果相关的基因和网络中的纯合缺失。
我们鉴定出了 170 个具有纯合缺失和相应表达缺失的基因。“细胞死亡”网络内的缺失呈过表达，并且具有这些缺失的病例总生存情况较差。对这些事件进行进一步分析后，我们生成了一个与 258 例患者较短生存相关的基于表达的特征，并在总计 800 例患者的两个独立组的数据中证实了该特征。我们定义了一个反映预后的 97 个细胞死亡基因的基因表达特征，并在两个独立的数据集中得到了验证。
我们从 97 个基因的特征中开发了一个简单的 6 个基因表达特征，可以用于在临床环境中识别预后不良的骨髓瘤。该特征可以作为未来旨在改善预后不良骨髓瘤患者预后的试验的基础。
