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Originally published as JCO Early Release 10.1200/JCO.2012.45.2011 on January 21 2014

Journal of Clinical Oncology, Vol 32, No 6 (February 20), 2014: pp. 579-586
© 2014 American Society of Clinical Oncology.

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BIOLOGY OF NEOPLASIA

Liquid Biopsies: Genotyping Circulating Tumor DNA

Luis A. Diaz, Jr, Alberto Bardelli

Luis A. Diaz Jr, Swim Across America Laboratory and Ludwig Center for Cancer Genetics and Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD; and Alberto Bardelli, Institute for Cancer Research and Treatment at Candiolo, University of Torino, Candiolo, and the Fondazione Italiana per la Ricerca sul Cancro Institute of Molecular Oncology, Milan, Italy.

Corresponding author: Alberto Bardelli, PhD, Laboratory of Molecular Genetics, Institute for Cancer Research and Treatment, Department of Oncology, University of Torino, Medical School, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy; e-mail: a.bardelli{at}unito.it.

Genotyping tumor tissue in search of somatic genetic alterations for actionable information has become routine practice in clinical oncology. Although these sequence alterations are highly informative, sampling tumor tissue has significant inherent limitations; tumor tissue is a single snapshot in time, is subject to selection bias resulting from tumor heterogeneity, and can be difficult to obtain. Cell-free fragments of DNA are shed into the bloodstream by cells undergoing apoptosis or necrosis, and the load of circulating cell-free DNA (cfDNA) correlates with tumor staging and prognosis. Moreover, recent advances in the sensitivity and accuracy of DNA analysis have allowed for genotyping of cfDNA for somatic genomic alterations found in tumors. The ability to detect and quantify tumor mutations has proven effective in tracking tumor dynamics in real time as well as serving as a liquid biopsy that can be used for a variety of clinical and investigational applications not previously possible.

Supported by the European Union Seventh Framework Programme of the Colon Therapy Research Consortium (Grant No. 259015); by the Associazione Italiana per la Ricerca sul Cancro (AIRC) Investigator Grant No. 12812; by AIRC 2010 Special Program Molecular Clinical Oncology 5 per mille, Project No. 9970; by Fondazione Piemontese per la Ricerca sul Cancro 5 per mille 2010 Ministero della Salute; Ministero dell'Istruzione, dell'Università e della Ricerca (Progetti di Ricerca di Interesse Nazionale), and by Swim Across America.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.


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