The patterns and dynamics of genomic instability in metastatic pancreatic cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-10-27

AUTHORS

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-Donahue, P. Andrew Futreal

ABSTRACT

A timeline for pancreatic cancerChristine 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. More... »

PAGES

1109-1113

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  • Journal

    TITLE

    Nature

    ISSUE

    7319

    VOLUME

    467

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature09460

    DOI

    http://dx.doi.org/10.1038/nature09460

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1022310913

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20981101


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