Skip to main content

mFast-SeqS as a Monitoring and Pre-screening Tool for Tumor-Specific Aneuploidy in Plasma DNA

  • Conference paper
  • First Online:
Circulating Nucleic Acids in Serum and Plasma – CNAPS IX

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Diaz LA Jr, Bardelli A (2014) Liquid biopsies: genotyping circulating tumor DNA. J Clin Oncol 32:579–586

    Article  PubMed  PubMed Central  Google Scholar 

  • 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.

    Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heitzer E, Auer M, Ulz P et al (2013c) Circulating tumor cells and DNA as liquid biopsies. Genome Med 5:73–83

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  PubMed  PubMed Central  Google Scholar 

  • 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

    Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of Interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ellen Heitzer .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this paper

Cite this paper

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

Download citation

Publish with us

Policies and ethics