Distant Metastasis Occurs Late during the Genetic Evolution of Pancreatic Cancer

By S. Yachida, Siân Jones, I. Bozic, T. Antal, R. Leary, Baojin Fu, Mihoko Kamiyama, R. Hruban, J. Eshleman, Martin A. Nowak and 4 more. Nature, 2010

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Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, 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. 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.

Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/85b937f4f026754b5dfcbbad7e07d24b9a581283

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Citations in the corpus

Intratumor heterogeneity: evolution through space and time. (2012, background): “In an extensive analysis of ITH in pancreatic cancer, Yachida and colleagues showed that clonal tumor populations present in the primary, but genetically distinct from the nonmetastatic clones, give rise to metastatic disease in a branched evolutionary pattern, with "progressor mutations" common to ”
The cancer stem cell: premises, promises and challenges (2011, background): “Two recent studies on pancreatic cancer have done just tha”
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EMT and dissemination precede pancreatic tumor formation (2012, background): “Recent genetic studies examining low-passage cell lines or microdissected primary tumors and matched metastases have concluded that metastasis is a late event in human PDAC (Campbell et al., 2010; Yachida et al., 2010).”
The Life History of 21 Breast Cancers (2012, background): “…sampled within a patient at different times (Ding et al., 2012; Shah et al., 2009), from different sites (Campbell et al., 2010; Ding et al., 2010; Yachida et al., 2010), at hypermutable genomic loci (Campbell et al., 2008), or through single-cell isolation (Anderson et al., 2011; Navin et al.,…”