Liu Wennuan, Laitinen Sari, Khan Sofia, Vihinen Mauno, Kowalski Jeanne, Yu Guoqiang, Chen Li, Ewing Charles M, Eisenberger Mario A, Carducci Michael A, Nelson William G, Yegnasubramanian Srinivasan, Luo Jun, Wang Yue, Xu Jianfeng, Isaacs William B, Visakorpi Tapio, Bova G Steven
Nat Med. 2009 May;15(5):559-65. doi: 10.1038/nm.1944. Epub 2009 Apr 12.
Many studies have shown that primary prostate cancers are multifocal and are composed of multiple genetically distinct cancer cell clones. Whether or not multiclonal primary prostate cancers typically give rise to multiclonal or monoclonal prostate cancer metastases is largely unknown, although studies at single chromosomal loci are consistent with the latter case. Here we show through a high-resolution genome-wide single nucleotide polymorphism and copy number survey that most, if not all, metastatic prostate cancers have monoclonal origins and maintain a unique signature copy number pattern of the parent cancer cell while also accumulating a variable number of separate subclonally sustained changes. We find no relationship between anatomic site of metastasis and genomic copy number change pattern. Taken together with past animal and cytogenetic studies of metastasis and recent single-locus genetic data in prostate and other metastatic cancers, these data indicate that despite common genomic heterogeneity in primary cancers, most metastatic cancers arise from a single precursor cancer cell. This study establishes that genomic archeology of multiple anatomically separate metastatic cancers in individuals can be used to define the salient genomic features of a parent cancer clone of proven lethal metastatic phenotype.
许多研究表明，原发性前列腺癌是多灶性的，由多个基因上不同的癌细胞克隆组成。多克隆原发性前列腺癌是否通常会导致多克隆或单克隆前列腺癌转移在很大程度上尚不清楚，尽管在单个染色体位点的研究与后一种情况一致。在这里，我们通过高分辨率全基因组单核苷酸多态性和拷贝数调查表明，大多数（如果不是全部）转移性前列腺癌都起源于单克隆，并保留了亲代癌细胞独特的标志性拷贝数模式，同时还积累了数量可变的单独亚克隆持续变化。我们发现转移的解剖部位与基因组拷贝数变化模式之间没有关系。结合过去关于转移的动物和细胞遗传学研究以及前列腺癌和其他转移性癌症最近的单基因座遗传数据，这些数据表明，尽管原发性癌症中存在常见的基因组异质性，但大多数转移性癌症都源自单个前体癌细胞。这项研究表明，个体中多个解剖学上分离的转移性癌症的基因组考古学可用于定义具有致命转移性表型的亲代癌症克隆的显著基因组特征。
