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  3. Exploring Evolutionary Trajectories In Ovarian Cancer Patients By Longitudinal Analysis Of Ctdna.
  1. Home
  3. Exploring Evolutionary Trajectories In Ovarian Cancer Patients By Longitudinal Analysis Of Ctdna.

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Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA.

Oliver Kutz1,2,3,4,5,6,7,8,9,10, Stephan Drukewitz2,3,4,6,11,12, Alexander Krüger2,3,4,6,12

  • 1Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, 9169 Technische Universität Dresden , Dresden, Germany.

Clinical Chemistry and Laboratory Medicine
|April 5, 2024

View abstract on PubMed

Summary
This summary is machine-generated.

Temporal heterogeneity of cell-free DNA (ctDNA) reveals ovarian cancer evolution. Tracing ctDNA identifies two distinct evolutionary patterns, aiding in targeting relapse-seeding clones for therapy.

Keywords:
ctDNAliquid biopsyovarian cancertumor evolution

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Area of Science:

  • Oncology
  • Genomics
  • Cancer Evolution

Background:

  • Ovarian cancer evolution and relapse dynamics are complex.
  • Understanding clonal heterogeneity is crucial for effective treatment strategies.

Purpose of the Study:

  • To analyze if temporal heterogeneity of cell-free DNA (ctDNA) encodes evolutionary patterns in ovarian cancer.
  • To identify distinct evolutionary patterns of ovarian cancer relapse.

Main Methods:

  • Targeted sequencing of 275 cancer-associated genes in primary tumor biopsies and longitudinal ctDNA samples from 15 ovarian cancer patients.
  • Utilized Illumina sequencing platform for high-resolution mutational analysis.

Main Results:

  • Low concordance between primary tumor and ctDNA mutational spectra, with TP53 variants being the most shared alterations.
  • Identified two distinct evolutionary patterns of relapse based on ctDNA clonal tracing: persistent ancestral clones and chemotherapy-cleared clones.
  • Observed ctDNA private variants, some indicating subclonal expansions post-chemotherapy.

    • Conclusions:

    • Temporal ctDNA heterogeneity analysis deciphers ovarian cancer evolutionary trajectories, even at sub-exome resolution.
    • Two identified evolutionary patterns can help pinpoint relapse-seeding clones for targeted therapeutic interventions.