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When Tissue Is Not Available in Liver Cancer, What About Plasma-Based Molecular Profiling?

By: Amanda E. Ruffino, BA
Posted: Tuesday, November 14, 2023

James J. Harding, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues aimed to investigate the potential of next-generation sequencing of circulating cell-free DNA for diagnosing, prognosticating, and treating advanced hepatocellular carcinoma. Their research, published in JCO Precision Oncology, identified key genomic alterations in cell-free DNA and assessed the agreement between cell-free DNA and tissue-based genotyping in patients with advanced hepatocellular carcinoma.

“The high detection rate of genetic alterations in cell-free DNA with overall high concordance supports the use of plasma-based molecular profiling where tissue acquisition is not feasible,” the investigators stated.

In this single-center, retrospective study, cell-free DNA from 53 plasma samples of 51 patients with confirmed hepatocellular carcinoma was analyzed using a 129-gene next-generation sequencing assay. The primary findings revealed genomic alterations in 92.2% of patients, with the most frequently mutated genes being TERT promoter, TP53, CTNNB1, ARID1A, and TSC2. Of note, 73% of patients had paired tumor next-generation sequencing, and the concordance between cell-free DNA and tumor tissue mutations was high for TERT, TP53, CTNNB1, ARID1A, and TSC2. In some cases (27%), cell-free DNA analysis detected alterations not found in the matched tumor tissue. Moreover, actionable mutations were identified in 37% of cases, including alterations in TSC1/2, BRCA1/2, and PIK3CA. The investigators also found that a higher average variant allele fraction was associated with elevated alpha-fetoprotein levels, increased tumor volume, and the absence of prior systemic therapy. However, it did not seem to correlate with overall survival in treatment-naive patients.

Overall, tumor mutation profiling of cell-free DNA in hepatocellular carcinoma may serve as a valuable alternative to tissue-based genomic profiling. However, the study suggests that for comprehensive detection of clinically actionable genomic alterations, it may be necessary to perform both blood and tumor sequencing.

Disclosure: For full disclosures of the study authors, visit

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