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Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
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Circulating Tumor DNA Profiling of Advanced Biliary Tract Cancers.

Kabir Mody1, Pashtoon M Kasi1, JuDong Yang2

  • 1Mayo Clinic, Jacksonville, FL.

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Summary

This study analyzed circulating tumor DNA (ctDNA) in biliary tract cancers (BTC), finding therapeutically relevant genomic alterations in over half of patients. This research supports ctDNA testing feasibility in BTC for potential treatment guidance.

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Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genomics

Background:

  • Noninvasive molecular diagnostics, such as circulating tumor DNA (ctDNA) profiling, are advancing the evaluation of solid tumors.
  • Biliary tract cancers (BTC) represent a group of malignancies with limited current data regarding ctDNA analysis.

Purpose of the Study:

  • To characterize the genomic alteration landscape of ctDNA in patients diagnosed with biliary tract cancers (BTC).
  • To assess the feasibility and findings of ctDNA testing in a cohort of BTC patients.

Main Methods:

  • 124 patients with BTC underwent ctDNA testing using a 73-gene panel assay between January 2015 and February 2018.
  • The assay targeted somatic genomic alterations, including mutations, amplifications, fusions, and indels.
  • Variants of unknown significance were excluded from the analysis.

Main Results:

  • 138 samples were analyzed, with 76% harboring at least one genomic alteration after excluding variants of unknown significance.
  • Therapeutically relevant alterations were identified in 55% of patients, including BRAF mutations, ERBB2 amplifications, FGFR2 fusions/mutations, and IDH1 mutations.
  • A distinct spectrum of alterations was noted between early-onset and older BTC patient groups.

Conclusions:

  • This study represents the largest reported cohort to date investigating ctDNA in BTC.
  • The findings demonstrate the feasibility of ctDNA testing in biliary tract cancers.
  • This research provides a foundational dataset for future studies in the field of ctDNA in BTC.