Circulating Tumor DNA Profiling of Advanced Biliary Tract Cancers

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.