Christine Iacobuzio-Donahue及其同事利用全基因组“外显子组”测序来分析来自相同患者的原发胰腺癌和一种或多种转移肿瘤。他们发现肿瘤由截然不同的亚克隆组成，确定了转移性癌症克隆在原发肿瘤内演化的演化图，并且估计了肿瘤发展的时间尺度。
基于这些数据他们估计，在胰腺肿瘤发生的开始和原发的、非转移性肿瘤的形成之间的平均时间为11.8年，而指示性转移克隆的出现另需6.8年。这些数据表明存在一个潜在很大的机会窗口，在此时段内也许有可能相对较早地检测出癌症来。
Peter Campbell及其同事利用下一代测序方法检测了13名胰腺癌患者的染色体重排。结果显示患者间存在相当大的异质性，表明在转移的发生过程中基因组不稳定和演化是持续存在的。但对所研究的大部分患者来说，所发现的基因重排中超过一半存在于所有转移肿瘤和原发肿瘤中，从而使其成为在这种疾病的早期和晚期进行治疗干预的潜在目标。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi:10.1038/nature09460
The patterns and dynamics of genomic instability in metastatic pancreatic cancer
Peter J. Campbell,Shinichi Yachida,Laura J. Mudie,Philip J. Stephens,Erin D. Pleasance,Lucy A. Stebbings,Laura A. Morsberger,Calli Latimer,Stuart McLaren,Meng-Lay Lin,David J. McBride,Ignacio Varela,Serena A. Nik-Zainal,Catherine Leroy,Mingming Jia,Andrew Menzies,Adam P. Butler,Jon W. Teague,Constance A. Griffin,John Burton,Harold Swerdlow,Michael A. Quail,Michael R. Stratton,Christine Iacobuzio-Donahueciacobu@jhmi.edu& P. Andrew Futrealpaf@sanger.ac.uk
Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97–98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations1, 2, 3, 4, 5, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours6, 7, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites7, and how the tumour disseminates. Here we harness advances in DNA sequencing8, 9, 10, 11, 12 to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2–M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.
