A comparative analysis of tissue-based and liquid-based next-generation sequencing in patients with anaplastic thyroid carcinoma

Ongoing progress in high-throughput next-generation sequencing (NGS) has enabled clinicians to comprehensively characterize the genomic landscape of tumors, guide treatment decisions, and facilitate clinical trial enrollment. The role of liquid NGS in anaplastic thyroid carcinoma (ATC) remains unclear, particularly in cases where tissue NGS is not feasible or yields inadequate results. Among these, 26 patients had adequate tissue for commercially available tissue NGS (ACTOnco®+, 440 genes), 15 had access to a commercially available liquid NGS platform (ACTMonitor®+, 50 genes), and 13 patients underwent both tissue and liquid NGS. The genetic alterations observed in ATC exhibited a high degree of heterogeneity, involving several pathways, including RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, cell cycle regulation, other receptor tyrosine kinases, DNA damage response, DNA mismatch repair (MMR, 34.6%, including MLH1, MSH6, MSH2, and PMS1), and chromatin remodeling. The most frequently mutated genes in tissue NGS were TP53 (17/26, 65.4%) and BRAF (8/26, 30.8%). Among the 13 pairs analyzed on both platforms, the concordance rates were 84.6% and 69.2% for BRAF and TP53, respectively. Among two patients without sufficient tissue for NGS, liquid NGS provided additional information on genetic alterations. NGS platforms, whether applied to tissue or liquid samples, can empower clinicians to identify targetable oncogenic events in ATC. Liquid biopsy provides supplementary information when the tissue is insufficient for NGS. Overall design: ATC patients provided adequate tissue samples for analysis using commercially available tissue-based, liquid-based NGS, or both. The study aimed to assess the frequency of established genetic events in tumorigenesis, identify potential novel driver mutations, and characterize candidates for targeted therapy. Additionally, it examined the concordance between tissue and liquid NGS results in ATC cases.