Advancing a clinically relevant perspective of the clonal nature of cancer

Christian Ruiz, Elizabeth Lenkiewicz, Lisa Evers, Tara Holley, Alex Robeson, Jeffrey Kiefer, Michael J. Demeure, Michael A. Hollingsworth, Michael Shen, Donna Prunkard, Peter S. Rabinovitch, Tobias Zellweger, Spyro Mousses, Jeffrey M. Trent, John D. Carpten, Lukas Bubendorf, Daniel Von Hoff, Michael Barrett

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Cancers frequently arise as a result of an acquired genomic instability and the subsequent clonal evolution of neoplastic cells with variable patterns of genetic aberrations. Thus, the presence and behaviors of distinct clonal populations in each patient's tumor may underlie multiple clinical phenotypes in cancers. We applied DNA content-based flow sorting to identify and isolate the nuclei of clonal populations from tumor biopsies, which was coupled with array CGH and targeted resequencing. The results produced high-definition genomic profiles of clonal populations from 40 pancreatic adenocarcinomas and a set of prostate adenocarcinomas, including serial biopsies from a patient who progressed to androgen-independent metastatic disease. The genomes of clonal populations were found to have patient-specific aberrations of clinical relevance. Furthermore, we identified genomic aberrations specific to therapeutically responsive and resistant clones arising during the evolution of androgen-independent metastatic prostate adenocarcinoma. We also distinguished divergent clonal populations within single biopsies and mapped aberrations in multiple aneuploid populations arising in primary and metastatic pancreatic adenocarcinoma. We propose that our high-definition analyses of the genomes of distinct clonal populations of cancer cells in patients in vivo can help guide diagnoses and tailor approaches to personalized treatment.

Original languageEnglish (US)
Pages (from-to)12054-12059
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number29
DOIs
StatePublished - Jul 19 2011
Externally publishedYes

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Adenocarcinoma
Population
Neoplasms
Biopsy
Androgens
Prostate
Genome
Clonal Evolution
Genomic Instability
Aneuploidy
Clone Cells
Phenotype
DNA
Therapeutics

Keywords

  • Clonal genomics
  • Pancreatic cancer
  • Prostate cancer

ASJC Scopus subject areas

  • General

Cite this

Advancing a clinically relevant perspective of the clonal nature of cancer. / Ruiz, Christian; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Robeson, Alex; Kiefer, Jeffrey; Demeure, Michael J.; Hollingsworth, Michael A.; Shen, Michael; Prunkard, Donna; Rabinovitch, Peter S.; Zellweger, Tobias; Mousses, Spyro; Trent, Jeffrey M.; Carpten, John D.; Bubendorf, Lukas; Von Hoff, Daniel; Barrett, Michael.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 29, 19.07.2011, p. 12054-12059.

Research output: Contribution to journalArticle

Ruiz, C, Lenkiewicz, E, Evers, L, Holley, T, Robeson, A, Kiefer, J, Demeure, MJ, Hollingsworth, MA, Shen, M, Prunkard, D, Rabinovitch, PS, Zellweger, T, Mousses, S, Trent, JM, Carpten, JD, Bubendorf, L, Von Hoff, D & Barrett, M 2011, 'Advancing a clinically relevant perspective of the clonal nature of cancer', Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 29, pp. 12054-12059. https://doi.org/10.1073/pnas.1104009108
Ruiz, Christian ; Lenkiewicz, Elizabeth ; Evers, Lisa ; Holley, Tara ; Robeson, Alex ; Kiefer, Jeffrey ; Demeure, Michael J. ; Hollingsworth, Michael A. ; Shen, Michael ; Prunkard, Donna ; Rabinovitch, Peter S. ; Zellweger, Tobias ; Mousses, Spyro ; Trent, Jeffrey M. ; Carpten, John D. ; Bubendorf, Lukas ; Von Hoff, Daniel ; Barrett, Michael. / Advancing a clinically relevant perspective of the clonal nature of cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 29. pp. 12054-12059.
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