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Realizing the potential of plasma genotyping in an age of genotype-directed therapies

Jason J Luke1, Geoffrey R Oxnard1, Cloud P Paweletz1

  • 1Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA (JJL, GRO, CPP, BEJ), Memorial Sloan-Kettering Cancer Center, New York, NY (DBS), University of Colorado Cancer Center, Denver, CO (DRC); The University of Texas MD Anderson Cancer Center, Houston, TX (JVH).

Journal of the National Cancer Institute
|August 10, 2014
PubMed

Insights

Plasma genotyping using cell-free DNA (cfDNA) offers a less invasive alternative to tumor biopsies for cancer treatment selection. Further validation and standardization of cfDNA assays are crucial for clinical application.

Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genetics

Background:

  • Genotype-directed cancer therapies, like EGFR and BRAF inhibitors, are increasingly used.
  • Traditional tumor biopsies are invasive and burdensome for patients.
  • Noninvasive plasma genotyping is gaining interest as an alternative.

Purpose of the Study:

  • To review and provide recommendations on cell-free DNA (cfDNA) plasma genotyping assays.
  • To discuss the development and clinical application of these emerging technologies.

Main Methods:

  • Review of technologies for cfDNA analysis, including allele-specific PCR, COLD PCR, emulsion PCR, and massively parallel sequencing.
  • Consensus commentary from the Cell Free DNA Working Group.

Main Results:

  • cfDNA genotyping presents a convenient and rapid alternative to tumor biopsies.
  • Several cfDNA analysis technologies are under development.
  • Clinical validity and utility require further evaluation in prospective trials.

Conclusions:

  • Standardization of cfDNA assays is critical for routine clinical practice.
  • Prospective trials are needed to establish assay validity and utility for predicting treatment efficacy and patient outcomes.
  • The Cell Free DNA Working Group offers recommendations for the use and interpretation of cfDNA plasma genotyping assays in research.

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