Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Shinichi Yachida, Sian 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, Christine A. Iacobuzio-Donahue

Research output: Contribution to journalArticlepeer-review

Abstract

Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated(1,2), is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy(3). Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.

Original languageEnglish
Pages (from-to)1114-1117
Number of pages6
JournalNature
Volume467
Issue number7319
DOIs
Publication statusPublished - 28 Oct 2010

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