The clonal evolution of metastases from primary serous epithelial ovarian cancers
The clonal evolution of metastases from primary serous epithelial ovarian cancers
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DOI：
10.1002/ijc.24148
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发表时间：
2009-04-01
影响因子：
6.4
通讯作者：
Ramus, Susan J.
中科院分区：
文献类型：
--
作者：
Khalique, Lalarukh;Ayhan, Ayse;Ramus, Susan J.
已经提出了从原发性癌症到转移的几种进化模型；但最被广泛接受的是结肠直肠癌的克隆进化模型，其中肿瘤的发展是由体细胞遗传改变积累驱动的线性克隆进化过程。癌症进展和转移的各种其他模型已经被提出，包括平行进化和相同的基因模型。本研究的目的是研究22例诊断为高级别浆液上皮性卵巢癌的原发癌转移的演变。我们在原发肿瘤和转移性沉积的肿瘤组织的几个不同区域建立了基于杂合性缺失模式的体细胞遗传谱。最大简约树分析用于检查每个患者的原发和转移样本之间的进化关系。此外，我们还研究了转移性肿瘤与原发性卵巢肿瘤之间的遗传异质性程度。我们的数据表明，大多数（如果不是全部的话）转移与原发肿瘤有克隆关系。然而，这些数据反对线性克隆进化的单一模型，即原发性肿瘤内的晚期克隆获得额外的遗传变化，使转移进展成为可能。相反，这些数据支持一个模型，其中原发性卵巢癌具有共同的克隆起源，但成为多克隆，在遗传分化的早期和晚期，不同的克隆获得进展到转移的能力。(C) 2008 Wiley-Liss, Inc。
Several models of evolution from primary cancers to metastases have been proposed; but the most widely accepted is the clonal evolution model proposed for colorectal cancer in which tumors develop by a process of linear clonal evolution driven by the accumulation of somatic genetic alterations. Various other models of cancer progression and metastasis have been proposed, including parallel evolution and the same gene model. The aim of this study was to investigate the evolution of metastases from primary cancer in 22 patients diagnosed with high-grade serous epithelial ovarian cancer. We established somatic genetic profiles based on the pattern of loss of heterozygosity, in several different regions of tumor tissue within the primary tumor and metastatic deposits front each case. Maximum parsimony tree analysis was used to examine the evolutionary relationship between the primary and metastatic samples for each patient. In addition, we investigated the extent of genetic heterogeneity within and between metastatic tumors compared with primary ovarian tumors. Our data suggest that most, if not all, metastases are clonally related to the primary tumors. However, the data oppose a single model of linear-clonal evolution whereby a late stage clone within the primary tumor acquires additional genetic changes that enable metastatic progression. Instead, the data support a model in which primary ovarian cancers have a common clonal origin, but become polyclonal, with different clones at both early and late stages of genetic divergence acquiring the ability to progress to metastasis. (C) 2008 Wiley-Liss, Inc.