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Updated: May 15, 2026

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A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Tumor Mutational Concordance and Recurrence Timing in Hepatocellular Carcinoma
Yuya Miura1,2,3, Ryo Ashida1, Keiichi Ohshima4
1Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
Summary
Genomic profiling reliably distinguishes true hepatocellular carcinoma (HCC) recurrence from multicentric recurrence. Recurrence timing alone is insufficient for accurate classification, highlighting the need for mutational analysis in HCC management.
Area of Science:
- Oncology
- Genomics
- Hepatobiliary Surgery
Background:
- Hepatocellular carcinoma (HCC) recurrence presents diagnostic challenges, with true recurrence (clonal relapse) and multicentric recurrence (de novo tumorigenesis) often difficult to differentiate based solely on timing.
- The accuracy of recurrence timing in distinguishing these subtypes of intrahepatic recurrence remains uncertain.
Purpose of the Study:
- To classify recurrent HCC tumors using somatic mutational concordance.
- To evaluate the validity of recurrence timing as a diagnostic criterion.
Main Methods:
- Whole-exome sequencing of paired primary and recurrent HCC tumors from 49 patients.
- Classification of true recurrence based on ≥ 10 shared somatic mutations.
- Quantification of mutational concordance using shared variant counts and Jaccard similarity index.
Main Results:
- 22 (44.9%) patients had true recurrence, and 27 (55.1%) had multicentric recurrence.
- True recurrence showed significantly higher mutational concordance (median 115 shared variants, Jaccard index 0.44) compared to multicentric recurrence (median 0 shared variants, Jaccard index 0.00).
- Recurrence timing showed inconsistent correlation with mutational concordance, though a 3-year cutoff provided significant separation.
Conclusions:
- Recurrence timing alone is inadequate for distinguishing between true and multicentric HCC recurrence.
- Genomic profiling provides a robust method for classifying HCC recurrence and informing clinical management strategies.
