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The patterns and dynamics of genomic instability in metastatic pancreatic cancer

Author

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  • Peter J. Campbell

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    University of Cambridge, Cambridge CB2 2XY, UK)

  • Shinichi Yachida

    (Johns Hopkins Medical Institutions)

  • Laura J. Mudie

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Philip J. Stephens

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Erin D. Pleasance

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Lucy A. Stebbings

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Laura A. Morsberger

    (Johns Hopkins Medical Institutions)

  • Calli Latimer

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Stuart McLaren

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Meng-Lay Lin

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • David J. McBride

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Ignacio Varela

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Serena A. Nik-Zainal

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Catherine Leroy

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Mingming Jia

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Andrew Menzies

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Adam P. Butler

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Jon W. Teague

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Constance A. Griffin

    (Johns Hopkins Medical Institutions)

  • John Burton

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Harold Swerdlow

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Michael A. Quail

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

  • Michael R. Stratton

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK
    Institute for Cancer Research, Sutton, Surrey SM2 5NG, UK)

  • Christine Iacobuzio-Donahue

    (Johns Hopkins Medical Institutions)

  • P. Andrew Futreal

    (Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK)

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.

Suggested Citation

  • 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. McBr, 2010. "The patterns and dynamics of genomic instability in metastatic pancreatic cancer," Nature, Nature, vol. 467(7319), pages 1109-1113, October.
  • Handle: RePEc:nat:nature:v:467:y:2010:i:7319:d:10.1038_nature09460
    DOI: 10.1038/nature09460
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    Cited by:

    1. Amr M. Al-Zain & Mattie R. Nester & Iffat Ahmed & Lorraine S. Symington, 2023. "Double-strand breaks induce inverted duplication chromosome rearrangements by a DNA polymerase δ-dependent mechanism," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Sun Young Lee & Farhan Haq & Deokhoon Kim & Cui Jun & Hui-Jong Jo & Sung-Min Ahn & Won-Suk Lee, 2014. "Comparative Genomic Analysis of Primary and Synchronous Metastatic Colorectal Cancers," PLOS ONE, Public Library of Science, vol. 9(3), pages 1-9, March.
    3. Chaohui Li & Lingxi Chen & Guangze Pan & Wenqian Zhang & Shuai Cheng Li, 2023. "Deciphering complex breakage-fusion-bridge genome rearrangements with Ambigram," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Bo Jiang & Xiaozhi Zhao & Wei Chen & Wenli Diao & Meng Ding & Haixiang Qin & Binghua Li & Wenmin Cao & Wei Chen & Yao Fu & Kuiqiang He & Jie Gao & Mengxia Chen & Tingsheng Lin & Yongming Deng & Chao Y, 2022. "Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Linda K Sundermann & Jeff Wintersinger & Gunnar Rätsch & Jens Stoye & Quaid Morris, 2021. "Reconstructing tumor evolutionary histories and clone trees in polynomial-time with SubMARine," PLOS Computational Biology, Public Library of Science, vol. 17(1), pages 1-28, January.
    6. Mihoko Saito-Adachi & Natsuko Hama & Yasushi Totoki & Hiromi Nakamura & Yasuhito Arai & Fumie Hosoda & Hirofumi Rokutan & Shinichi Yachida & Mamoru Kato & Akihiko Fukagawa & Tatsuhiro Shibata, 2023. "Oncogenic structural aberration landscape in gastric cancer genomes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Cheng H Lee & Benjamin O Alpert & Preethi Sankaranarayanan & Orly Alter, 2012. "GSVD Comparison of Patient-Matched Normal and Tumor aCGH Profiles Reveals Global Copy-Number Alterations Predicting Glioblastoma Multiforme Survival," PLOS ONE, Public Library of Science, vol. 7(1), pages 1-11, January.
    8. Sanjay M. Prakadan & Christopher A. Alvarez-Breckenridge & Samuel C. Markson & Albert E. Kim & Robert H. Klein & Naema Nayyar & Andrew W. Navia & Benjamin M. Kuter & Kellie E. Kolb & Ivanna Bihun & Jo, 2021. "Genomic and transcriptomic correlates of immunotherapy response within the tumor microenvironment of leptomeningeal metastases," Nature Communications, Nature, vol. 12(1), pages 1-10, December.

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