Abstract
Recent progress in the analysis of cell-free DNA fragments (cell-free circulating tumor DNA, ctDNA) now allows monitoring of tumor genomes by non-invasive means. However, previous studies with plasma DNA from patients with cancer demonstrated highly variable allele frequencies of ctDNA. Comprehensive genome-wide analysis of tumor genomes is greatly facilitated when plasma DNA has increased amounts of ctDNA. In order to develop a fast and cost-effective pre-screening method for the identification of plasma samples suitable for further extensive qualitative analysis, we adapted the recently described FAST-SeqS method. We show that our modified FAST-SeqS method (mFAST-SeqS) can be used as a pre-screening tool for an estimation of the ctDNA percentage. Moreover, since the genome-wide mFAST-SeqS z-scores correlate with the actual tumor content in plasma samples, changes in ctDNA levels associated with response to treatment can be easily monitored without prior knowledge of the genetic composition of tumor samples.
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References
Belic J, Koch M, Ulz P et al (2015) Rapid identification of plasma DNA samples with increased ctDNA levels by a modified FAST-SeqS approach. Clin Chem 61:838–849
Bettegowda C, Sausen M, Leary RJ et al (2014) Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med 6:224ra24
Chan KC, Jiang P, Chan CW et al (2013a) Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc Natl Acad Sci U S A 110:18761–18768
Chan KC, Jiang P, Zheng YW et al (2013b) Cancer genome scanning in plasma: detection of tumor-associated copy number aberrations, single-nucleotide variants, and tumoral heterogeneity by massively parallel sequencing. Clin Chem 59:211–224
Diaz LA Jr, Bardelli A (2014) Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 32:579–586
Forshew T, Murtaza M, Parkinson C et al (2012) Noninvasive identification and monitoring of cancer mutations by targeted deep sequencing of plasma DNA. Sci Transl Med 4:136ra168.
Heidary M, Ulz P, Heitzer E et al (2014) The dynamic range of circulating tumor DNA in metastatic breast cancer. Breast Cancer Res 16:421–430
Heitzer E, Auer M, Gasch C et al (2013a) Complex tumor genomes inferred from single circulating tumor cells by array-CGH and next-generation sequencing. Cancer Res 73:2965–2975
Heitzer E, Auer M, Hoffmann EM et al (2013b) Establishment of tumor-specific copy number alterations from plasma DNA of patients with cancer. Int J Cancer 133:346–356
Heitzer E, Auer M, Ulz P et al (2013c) Circulating tumor cells and DNA as liquid biopsies. Genome Med 5:73–83
Heitzer E, Ulz P, Belic J et al (2013d) Tumor-associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing. Genome Med 5:30–45
Kinde I, Papadopoulos N, Kinzler KW et al (2012) FAST-SeqS: a simple and efficient method for the detection of aneuploidy by massively parallel sequencing. PLoS ONE 7:e41162
Leary RJ, Sausen M, Kinde I et al (2012) Detection of chromosomal alterations in the circulation of cancer patients with whole-genome sequencing. Sci Transl Med 4:162ra154
Lianidou ES, Strati A, Markou A (2014) Circulating tumor cells as promising novel biomarkers in solid cancers. Crit Rev Clin Lab Sci 51(3):160–171
Lim SH, Becker TM, Chua W et al (2014) Circulating tumour cells and circulating free nucleic acid as prognostic and predictive biomarkers in colorectal cancer. Cancer Lett 346:24–33
Mohan S, Heitzer E, Ulz P et al (2014) Changes in colorectal carcinoma genomes under anti-EGFR therapy identified by whole-genome plasma DNA sequencing. PLoS Genet 10:e1004271
Murtaza M, Dawson S, Tsui DWY (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA. Nature 497:108–112
Thierry AR, Mouliere F, El Messaoudi S et al (2014) Clinical validation of the detection of KRAS and BRAF mutations from circulating tumor DNA. Nat Med 20:430–435
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Belic, J. et al. (2016). mFast-SeqS as a Monitoring and Pre-screening Tool for Tumor-Specific Aneuploidy in Plasma DNA. In: Gahan, P., Fleischhacker, M., Schmidt, B. (eds) Circulating Nucleic Acids in Serum and Plasma – CNAPS IX. Advances in Experimental Medicine and Biology, vol 924. Springer, Cham. https://doi.org/10.1007/978-3-319-42044-8_28
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DOI: https://doi.org/10.1007/978-3-319-42044-8_28
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