Circulating Cell-Free DNA-Based Comprehensive Molecular Analysis of Biliary Tract Cancers Using Next-Generation...

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Biliary tract cancer (BTC) is a rare, aggressive malignancy with a poor prognosis and limited second-line treatment options.
• Precision oncology relies on identifying specific molecular alterations to guide targeted therapies.
• Next-generation sequencing (NGS) is crucial for detecting these mutations.

Purpose of the Study:

• To identify somatic mutations and tumor variant burden (TVB) in both cell-free DNA (cfDNA) from liquid biopsies (LB) and matched tumor tissue.
• To evaluate the utility of LB as a minimally invasive tool for molecular profiling in BTC.
• To correlate cfDNA yield with tumor volume and assess the detection of key BTC aberrations.

Main Methods:

• Prospective study analyzing cfDNA from peripheral blood liquid biopsies and matched tumor tissue.
• Utilized NGS to identify somatic mutations and calculate TVB.
• Correlated cfDNA yield with estimated tumor volume.

Main Results:

• A strong positive correlation was found between estimated tumor volume and cfDNA yield (r = 0.9326, p < 0.0001).
• Similar TVB was observed between liquid biopsy and tissue samples.
• Single nucleotide variants (SNVs) were detected in 84% of cases, with LB being informative in two cases where tissue analysis was not.
• Key BTC-associated mutations (FGFR2, IDH1, IDH2, KRAS, TP53) were detectable in matched LB samples.

Conclusions:

• Liquid biopsy offers a minimally invasive approach to identify critical molecular genetic alterations in cholangiocarcinoma and gallbladder cancers.
• cfDNA analysis captures significant tumor heterogeneity, providing valuable insights for precision oncology in BTC.
• This approach holds promise for advancing personalized treatment strategies for advanced BTC.