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Breast cancer intratumor genetic heterogeneity: causes and implications

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Ng, C. K. Y., Pemberton, H. N., Reis, J. S. (2012) Breast cancer intratumor genetic heterogeneity: causes and implications. EXPERT REVIEW OF ANTICANCER THERAPY, 12 (8). pp. 1021-1032. ISSN 1473-7140

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Abstract

There is burgeoning evidence to suggest that tumor evolution follows the laws of Darwinian evolution, whereby individual tumor cell clones harbor private genetic aberrations in addition to the founder mutations, and that these distinct populations of cancer cells interact in competitive and mutualistic manners. The combined effect of genetic and epigenetic instability, and differential selective pressures according to the microenvironment and therapeutic interventions, create many different evolutionary routes such that intratumor heterogeneity is inevitable. Numerous cytogenetic, comparative genomic hybridization and, more recently, massively parallel sequencing studies have generated indisputable evidence of this phenomenon. The impact of intratumor heterogeneity on response and resistance to therapy is beginning to be understood; this information may prove crucial for the potentials of personalized medicine to be realized. In this review, the evidence of intratumor heterogeneity in breast cancer, its potential causes and implications for the clinical management of breast cancer patients are discussed.

Item Type: Review Article
Authors (ICR Faculty only): Reis-Filho, Jorge
All Authors: Ng, C. K. Y., Pemberton, H. N., Reis, J. S.
Additional Information: ISI Document Delivery No.: 031PZ Times Cited: 0 Cited Reference Count: 108 Ng, Charlotte K. Y. Pemberton, Helen N. Reis-Filho, Jorge S. Breakthrough Breast Cancer; NHS CKY Ng, HN Pemberton and JS Reis-Filho are funded by Breakthrough Breast Cancer. The authors also acknowledge NHS funding for the National Institute of Health Research Biomedical Research Centre. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Expert reviews London
Uncontrolled Keywords: breast cancer clonal evolution drug resistance genomic instability intratumor heterogeneity island methylator phenotype chronic myeloid-leukemia kinase domain mutations lymph-node metastases ovarian carcinomas colorectal-cancer clonal evolution tumor-cells in-situ microsatellite instability
Research teams: Closed research groups > Molecular Pathology
Depositing User: Barry Jenkins
Date Deposited: 03 Jan 2013 15:17
Last Modified: 19 Feb 2014 16:24
URI: http://publications.icr.ac.uk/id/eprint/12126

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