Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Shinichi Yachida, Siân Jones, Ivana Bozic, Tibor Antal, Rebecca Leary, Baojin Fu, Mihoko Kamiyama, Ralph H. Hruban, James R. Eshleman, Martin A. Nowak, Victor E. Velculescu, Kenneth W. Kinzler, Bert Vogelstein and Christine A. Iacobuzio-Donahue ()
Additional contact information
Shinichi Yachida: The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions
Siân Jones: The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center
Ivana Bozic: Program for Evolutionary Dynamics, Harvard University
Tibor Antal: Program for Evolutionary Dynamics, Harvard University
Rebecca Leary: The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center
Baojin Fu: The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions
Mihoko Kamiyama: The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions
Ralph H. Hruban: The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions
James R. Eshleman: The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions
Martin A. Nowak: Program for Evolutionary Dynamics, Harvard University
Victor E. Velculescu: The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center
Kenneth W. Kinzler: The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center
Bert Vogelstein: The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute at The Johns Hopkins Kimmel Cancer Center
Christine A. Iacobuzio-Donahue: The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions

Nature, 2010, vol. 467, issue 7319, 1114-1117

Abstract: A timeline for pancreatic cancer Christine Iacobuzio-Donahue and colleagues use whole-genome exome sequencing to analyse primary pancreatic cancers and one or more metastases from the same patients, and find that tumours are composed of distinct subclones. The authors also determine the evolutionary maps by which metastatic cancer clones have evolved within the primary tumour, and estimate the timescales of tumour progression. On the basis of these data, they estimate a mean period of 11.8 years between the initiation of pancreatic tumorigenesis and the formation of the parental, non-metastatic tumour, and a further 6.8 years for the index metastasis clone to arise. These data point to a potentially large window of opportunity during which it might be possible to detect the cancer in a relatively early form. Peter Campbell and colleagues use next-generation sequencing to detect chromosomal rearrangements in 13 patients with pancreatic cancer. The results reveal considerable inter-patient heterogeneity and indicate ongoing genomic instability and evolution during the development of metastases. But for most of the patients studied, more than half of the genetic rearrangements found were present in all metastases and the primary tumour, making them potential targets for therapeutic intervention at early and late stages of the disease.

Date: 2010
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DOI: 10.1038/nature09515

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