Circulating tumor DNA as a non-invasive diagnostic and research tool.

Abstract:

Abstract In patients with solid malignancies, cell-free DNA carrying tumor-specific sequences can be found in body fluids such as blood plasma. This circulating tumor DNA (ctDNA) contains representation of the entire cancer genome, broken down into short mutation-carrying fragments, whose relative levels vary in response to treatment and progression. Different approaches to the study of ctDNA can work together to provide a window for noninvasive analysis of the cancer genome and its dynamics. Quantification of ctDNA levels may be useful as a prognostic biomarker and to assess response to treatment. When cancer overcomes treatment and progresses, the fraction of mutant alleles in plasma DNA can reach levels of 10%~20% or more, which makes it possible to study cancer evolution noninvasively by whole-genome or exome analysis of plasma DNA. Sensitivity and resistance to targeted therapies are often associated with known mutations in hotspot loci or genes. In advanced cancer patients, the status of pre-defined mutations can be analyzed noninvasively using circulating plasma DNA as a liquid biopsy. Targeted sequencing of limited regions in circulating DNA can allow identification of de novo mutations, even when these are present as rare fragments. This also facilitates parallel quantification of multiple mutations in plasma, which can indicate the relative systemic burden of different mutations or clones. Routine monitoring for sensitizing and resistance-conferring mutations may provide a framework for rational adaptive cancer therapy, providing real-time information on mutation levels to guide treatment against the most aggressive or treatable clones. Citation Format: Nitzan Rosenfeld. Circulating tumor DNA as a non-invasive diagnostic and research tool. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY11-03. doi:10.1158/1538-7445.AM2013-SY11-03

Authors:

N Rosenfeld

Journal:

Cancer Research

Citation info:

73(8_Supplement):sy11-03-sy11-03

Publication date:

15th Apr 2013

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