Advancing a clinically relevant perspective of the clonal nature of cancer
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 1195239
Author(s) 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 T
Author(s) at UniBasel Bubendorf, Lukas
Zellweger, Tobias
Year 2011
Title Advancing a clinically relevant perspective of the clonal nature of cancer
Journal Proceedings of the National Academy of Sciences of the United States of America
Volume 108
Number 29
Pages / Article-Number 12054-9
Keywords clonal genomics, pancreatic cancer, prostate cancer
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.
Publisher National Academy of Sciences
ISSN/ISBN 0027-8424
Full Text on edoc No
Digital Object Identifier DOI 10.1073/pnas.1104009108
PubMed ID
ISI-Number WOS:000292876900068
Document type (ISI) Journal Article

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