A metastasis or a second independent cancer? Evaluating the clonal origin of tumors using array copy number data.
A metastasis or a second independent cancer? Evaluating the clonal origin of tumors using array copy number data.
复制标题
DOI：
10.1002/sim.3866
复制
发表时间：
2010-07-10
影响因子：
2
通讯作者：
Begg, Colin B.
中科院分区：
文献类型：
--
作者：
Ostrovnaya, Irina;Olshen, Adam B.;Seshan, Venkatraman E.;Orlow, Irene;Albertson, Donna G.;Begg, Colin B.
当癌症患者发展出新的肿瘤时，有必要确定它是原始癌症的复发（转移）还是疾病的全新发生。这是通过评估病变的组织病理学来实现的。然而，在许多临床情况下，这种病理诊断是困难的。由于每种肿瘤的特征在于不同的体细胞突变模式，通过比较两种模式，在这些困难的临床情况下，原则上可以进行更明确的诊断。在这篇文章中，我们开发和评估的数据来自阵列拷贝数数据，旨在确定所有的体细胞等位基因的增益和损失的基因组时，这种比较的统计策略。首先，使用分割算法来估计等位基因增益和损失的区域。评估两种肿瘤之间的这些模式的相关性，并通过对单个染色体臂内的每个可能的克隆突变进行更精确的定量比较来补充。将结果组合以确定似然比，以区分克隆肿瘤对（转移）与独立的第二原发肿瘤。我们的数据分析表明，在许多情况下，一个强大的克隆信号出现。敏感性分析表明，当数据质量高时，大多数诊断是稳健的。
When a cancer patient develops a new tumor it is necessary to determine if it is a recurrence (metastasis) of the original cancer, or an entirely new occurrence of the disease. This is accomplished by assessing the histo-pathology of the lesions. However, there are many clinical scenarios in which this pathological diagnosis is difficult. Since each tumor is characterized by a distinct pattern of somatic mutations, a more definitive diagnosis is possible in principle in these difficult clinical scenarios by comparing the two patterns. In this article we develop and evaluate a statistical strategy for this comparison when the data are derived from array copy number data, designed to identify all of the somatic allelic gains and losses across the genome. First a segmentation algorithm is used to estimate the regions of allelic gain and loss. The correlation in these patterns between the two tumors is assessed, and this is complemented with more precise quantitative comparisons of each plausibly clonal mutation within individual chromosome arms. The results are combined to determine a likelihood ratio to distinguish clonal tumor pairs (metastases) from independent second primaries. Our data analyses show that in many cases a strong clonal signal emerges. Sensitivity analyses show that most of the diagnoses are robust when the data are of high quality.
登录
查看更多内容
影响因子：
2
作者：
Huang, J;Behrens, C;Jagirdar, J
通讯作者：
Jagirdar, J
影响因子：
--
作者：
Nestler, U.;Schmidinger, A.;Kuchelmeister, K. W.
通讯作者：
Kuchelmeister, K. W.
影响因子：
10.3
作者：
Bollet, Marc A.;Servant, Nicolas;Thiery, Jean-Paul
通讯作者：
Thiery, Jean-Paul
影响因子：
4
作者：
Knösel, T;Schlüns, K;Petersen, I
通讯作者：
Petersen, I
影响因子：
2.1
作者：
Olshen, AB;Venkatraman, ES;Wigler, M
通讯作者：
Wigler, M