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Capturing tumor heterogeneity and clonal evolution in solid cancers using circulating tumor DNA analysis.

Nieves Perdigones1, Muhammed Murtaza2

  • 1Center for Noninvasive Diagnostics, Translational Genomics Research Institute, Phoenix, AZ, USA.

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|February 8, 2017
PubMed
Summary
This summary is machine-generated.

Circulating tumor DNA (ctDNA) analysis offers a noninvasive method for tumor genotyping in metastatic cancer. While not always concordant with tissue biopsies, ctDNA can reveal tumor heterogeneity and clonal evolution for adaptive treatment strategies.

Keywords:
Cell-free DNACirculating tumor DNAClonal evolutionTreatment resistanceTumor heterogeneity

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Tissue biopsies are standard for tumor genotyping but can be invasive and may not reflect tumor heterogeneity.
  • Circulating tumor DNA (ctDNA) analysis presents a noninvasive alternative for genotyping, especially when biopsies are contraindicated or repeat analysis is needed.
  • Discordance between tissue and plasma ctDNA results requires careful interpretation, considering analytical limitations and biological factors.

Purpose of the Study:

  • To review the opportunities and limitations of ctDNA analysis in advanced cancers.
  • To explore the role of ctDNA in understanding tumor heterogeneity and subclonal evolution.
  • To discuss the clinical implications of ctDNA analysis for guiding adaptive treatment strategies.

Main Methods:

  • Literature review of recent studies on ctDNA analysis in advanced cancers.
  • Analysis of factors influencing tissue-plasma concordance in ctDNA testing.
  • Evaluation of ctDNA's utility in tracking tumor heterogeneity and subclonal evolution.

Main Results:

  • ctDNA analysis is a promising noninvasive tool for tumor genotyping in metastatic cancer.
  • Discordant results between tissue and ctDNA can arise from assay limitations or low tumor DNA levels in plasma.
  • When analytical issues are excluded, tissue-plasma concordance and quantitative ctDNA levels reflect tumor heterogeneity and can track clonal evolution.

Conclusions:

  • ctDNA analysis holds significant potential for noninvasive tumor genotyping and monitoring in advanced cancers.
  • Understanding tissue-plasma concordance is crucial for accurate clinical interpretation of ctDNA results.
  • Longitudinal ctDNA analysis can guide adaptive treatment by revealing subclonal evolution and tumor heterogeneity.