Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
Genomic signatures predict poor outcome in undifferentiated pleomorphic sarcomas and leiomyosarcomas.
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DOI：
10.1371/journal.pone.0067643
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rogatto SR
中科院分区：
文献类型：
--
作者：
Silveira SM;Villacis RA;Marchi FA;Barros Filho Mde C;Drigo SA;Neto CS;Lopes A;da Cunha IW;Rogatto SR
未分化的高级别多形性肉瘤（ups）表现出侵袭性临床行为，经常发生局部复发和远处转移。由于这些肉瘤通常与其他肿瘤具有相似的形态模式，特别是平滑肌肉瘤（lms），因此通常采用排除法进行分类。在这项研究中，基于阵列的比较基因组杂交（array CGH）用于分析来自未经治疗的患者的20个UPS和17个LMS样本。与UPS样品相比，LMS样品呈现出较低的基因组改变频率。最常改变的UPS区域涉及20q13.33和7q22.1的收益和3p26.3的损失。在LMS样品中经常检测到8q24.3和19q13.12位点的增益和9p21.3位点的损失。在这些区域中，1q21.3、11q12.2-q12.3、16p11.2和19q13.12的获益与LMS患者总生存时间的缩短显著相关。多变量分析显示，1q21.3的增益是LMS患者生存时间缩短的独立预后指标（HR = 13.76; P = 0.019）。虽然使用无监督分层聚类分析无法区分UPS和LMS样本的拷贝数谱，但三个聚类中的一个聚类呈现与预后不良相关的病例（P = 0.022）。采用实时荧光定量PCR技术对11份LMS和16份UPS样本中的ARNT、SLC27A3和PBXIP1基因进行相对拷贝数分析。在两种肿瘤类型中都观察到1q21-q22的增益，特别是在UPS样本中。这些发现为预测UPS和LMS患者预后不良的基因组特征的存在提供了强有力的证据。
Undifferentiated high-grade pleomorphic sarcomas (UPSs) display aggressive clinical behavior and frequently develop local recurrence and distant metastasis. Because these sarcomas often share similar morphological patterns with other tumors, particularly leiomyosarcomas (LMSs), classification by exclusion is frequently used. In this study, array-based comparative genomic hybridization (array CGH) was used to analyze 20 UPS and 17 LMS samples from untreated patients. The LMS samples presented a lower frequency of genomic alterations compared with the UPS samples. The most frequently altered UPS regions involved gains at 20q13.33 and 7q22.1 and losses at 3p26.3. Gains at 8q24.3 and 19q13.12 and losses at 9p21.3 were frequently detected in the LMS samples. Of these regions, gains at 1q21.3, 11q12.2-q12.3, 16p11.2, and 19q13.12 were significantly associated with reduced overall survival times in LMS patients. A multivariate analysis revealed that gains at 1q21.3 were an independent prognostic marker of shorter survival times in LMS patients (HR = 13.76; P = 0.019). Although the copy number profiles of the UPS and LMS samples could not be distinguished using unsupervised hierarchical clustering analysis, one of the three clusters presented cases associated with poor prognostic outcome (P = 0.022). A relative copy number analysis for the ARNT, SLC27A3, and PBXIP1 genes was performed using quantitative real-time PCR in 11 LMS and 16 UPS samples. Gains at 1q21-q22 were observed in both tumor types, particularly in the UPS samples. These findings provide strong evidence for the existence of a genomic signature to predict poor outcome in a subset of UPS and LMS patients.
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