edoc

Advancing a clinically relevant perspective of the clonal nature of cancer

Ruiz, Christian and Lenkiewicz, Elizabeth and Evers, Lisa and Holley, Tara and Robeson, Alex and Kiefer, Jeffrey and Demeure, Michael J. and Hollingsworth, Michael A. and Shen, Michael and Prunkard, Donna and Rabinovitch, Peter S. and Zellweger, Tobias and Mousses, Spyro and Trent, Jeffrey M. and Carpten, John D. and Bubendorf, Lukas and Von Hoff, Daniel and Barrett, Michael T.. (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. pp. 12054-12059.

Full text not available from this repository.

Official URL: http://edoc.unibas.ch/dok/A6005425

Downloads: Statistics Overview

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.
Faculties and Departments:03 Faculty of Medicine > Bereich Operative Fächer (Klinik) > Innere Organe
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Operative Fächer (Klinik) > Innere Organe
03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Stammzellpathologie (Bubendorf)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB > Stammzellpathologie (Bubendorf)
UniBasel Contributors:Bubendorf, Lukas and Zellweger, Tobias
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:National Academy of Sciences
ISSN:0027-8424
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:13 Sep 2013 07:59
Deposited On:13 Sep 2013 07:49

Repository Staff Only: item control page