CIRCULATING TUMOR DNA - DETECTION OF CTNNB1 MUTATIONS IN PLASMA FROM A DANISH COHORT OF HCC PATIENTS

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Introduction: Treatment and surveillance of hepatocellular carcinoma (HCC) is associated with significant costs, both financially and personally for the patient. Therefore, it is crucial to evaluate the clinical response to treatment thoroughly. We have yet to identify a biomarker able to detect progression, relapse or stable disease in HCC, but circulating tumor DNA (ctDNA) may be such a biomarker. Potential advantages are; easy accessibility, safety/non-invasive sampling, high specificity, possibility of sequential testing and circumvention of problems with tumor heterogeneity. The mutational landscape of HCC is dependent of the etiology of any preexisting liver disease, which varies substantially among different parts of the world. Previous studies on ctDNA in HCC arises from areas with a high prevalence of chronic hepatitis B. In Denmark, the etiology of liver cirrhosis and HCC is primarily alcohol consumption (ALC), hepatitis C (HCV) and non-alcoholic steatohepatitis (NASH). Additionally, an increasing number of elderly patients are diagnosed with HCC without underlying cirrhosis. CTNNB1, a gene in the β-catenin pathway, harbors mutations in up to 10-25 % of HCC tissue samples. It has yet to be established how this affects the prognosis. Until now, no targeted treatment against CTNNB1 mutations has been approved.
 Methods: Blood samples were obtained from HCC patients before treatment start (radiofrequency ablation (31%), resection (10%), transarterial chemoembolization (19%), Sorafenib (30%) or selective internal radiation therapy (4%)), 1 month and every 6 months after treatment. Some patients discontinued treatment before follow up (8.4%). Cell free DNA was purified from 4 mL plasma. The droplet digital PCR technique was used for detection of CTNNB1 c. 121A>G (p.T41A) mutated DNA fragments. Results: The study is ongoing. So far, we have included 84 HCC patients, 63 males (75%), mean age 69 (range 35-85). Etiology of cirrhosis and HCC is ALC alone n=31 (37%), ALC and HCV n=6 (8%), HCV alone n=7 (8%), NASH n=2 (2%), autoimmune n=4 (5%), hemochromatosis n=1 (1%), undetermined n=6 (7%) and non-cirrhosis n=27 (32%). Child Pugh stage: 26 stage A, 27 stage B and 4 stage C, and 27 non-cirrhotic patients. Barcelona Clinic Liver Cancer stage: 11 stage 0, 13 stage A, 9 stage B, 47 stage C, 4 stage D. Nine patients (11%) had detectable p.T41A mutation in CTNNB1 at baseline. One patient underwent resection and in follow up samples the mutation was undetectable and with no signs of relapse on simultaneous diagnostic imaging. One patient received radiofrequency ablation and had no detectable mutations in follow up samples. One patient remained positive after treatment with Sorafenib. One patient received transarterial chemoembolization and had a decline in amount of mutated DNA in follow up samples but the mutation were still detectable. The remaining five patients terminated treatment before follow up samples were obtained. Conclusion: ctDNA can be detected in a Danish cohort of patients with HCC with alcohol as primary cirrhosis etiology. The frequency of patients harboring the CTNNB1 p.T41A mutation in their plasma corresponds to the preexisting literature and databases on genetic features of HCC tissue samples. The first steps towards an individualized surveillance and possible treatment has been taken. Further studies on larger cohorts and longer time of follow up is needed in order to determine whether ctDNA and the CTNNB1 p.T41A mutation can be used to predict the clinical course of HCC.
Original languageEnglish
Publication year15 Sep 2018
Number of pages1
Publication statusPublished - 15 Sep 2018
EventInternational Liver Cancer Association Annual Conference - Hilton London Metropole, London, United Kingdom
Duration: 14 Sep 201816 Sep 2018
https://www.ilca2018.org/

Conference

ConferenceInternational Liver Cancer Association Annual Conference
LocationHilton London Metropole
CountryUnited Kingdom
CityLondon
Period14/09/201816/09/2018
Internet address

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