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. 2021 Apr 8;21(1):376.
doi: 10.1186/s12885-021-08103-0.

Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

Stine Karlsen Oversoe  1   2 , Michelle Simone Clement  3 , Britta Weber  4 , Henning Grønbæk  5 , Stephen Jacques Hamilton-Dutoit  6 , Boe Sandahl Sorensen  3 , Jens Kelsen  5
Affiliations

Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

Stine Karlsen Oversoe et al. BMC Cancer. .

Abstract

Background and aims: Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC.

Methods: We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up.

Results: In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients.

Conclusion: Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

Keywords: Circulating tumor DNA; Droplet digital PCR; Hepatocellular carcinoma; Molecular pathology; Predictive biomarkers.

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Conflict of interest statement

The authors have nothing to disclose in relation to this manuscript.

Figures

Fig. 1
Fig. 1
Correlation between amount of CTNNB1-mutated alleles with 95% confidence intervals during follow up and clinical course of disease in five HCC patients. a Patient underwent resection and concomittant radiofrequency ablation. Relapse diagnosed on CT scans after 1 year. b Patient received sorafenib. Stopped treatment after 8 weeks because of progressive disease and declining performance status. c Patient underwent radiofrequency ablation with complete response. d Patient received Trans Arterial Chemo Embolization with a mixed response. e Patient recieved sorafenib. Stopped treatment due to declining performance status. Deceased after 6 months
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