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Monday, December 17, 2018 
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Implementing Circulating Tumor DNA in Oncology Clinical Practice

January-March 2017, Volume 12, Number 1
Joana Vidal, Alvaro Taus, Alba Dalmases and Clara Montagut
Cancer Research Program FIMIM, Hospital del Mar, Barcelona, Spain

An accurate molecular profiling of genomic alterations in solid malignances is nowadays mandatory to establish the best clinical and therapeutic approach in patients with advanced cancer. Moreover, during systemic treatment, pressure is exerted on the tumor cells with the evolution of different sub-clones and the emergence of new resistant alterations. The current standard of tissue biopsy at the time of diagnosis and, when possible, at time of progression is not always feasible or practical and may underestimate intra-tumor heterogeneity and tumor clonal dynamics. Circulating DNA fragments carrying tumor-specific sequence alterations (circulating tumor DNA) are released from cancer cells into blood, representing a variable and generally small fraction of the total circulating cell-free DNA. Tumor genotyping using circulating tumor DNA representing a non-invasive liquid biopsy offers potential advantages versus the standard practice of determining somatic mutation status of archival tumor tissue biopsies. Despite the low levels of circulating tumor DNA, technological advances in next generation sequencing and digital polymerase chain reaction technologies have led to dramatic improvements in variant detection sensitivity and specificity. These technologies allow the quantification of circulating tumor DNA, providing valuable information on both targetable mutations and capturing real-time variations in tumor dynamics. The aim of this work is to understand the biology and technical issues of the analysis of circulating tumor DNA and provide an overview of the main applications of liquid biopsies and the potential benefits of the implementation of circulating tumor DNA study in clinical practice.

Key words:
Circulating tumor DNA. ctDNA. Liquid biopsy. Clonal dynamics. Tumor heterogeneity.
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