Stine Karlsen Oversoe1,2, Michelle Simone Clement3, Britta Weber4, Henning Grønbæk5, Stephen Jacques Hamilton-Dutoit6, Boe Sandahl Sorensen3, Jens Kelsen5. 1. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. stinkarl@rm.dk. 2. Department of Internal Medicine, Randers Regional Hospital, Randers, Denmark. stinkarl@rm.dk. 3. Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark. 4. Department of Clinical Oncology and Danish Centre of Particle Therapy, Aarhus University Hospital, Aarhus, Denmark. 5. Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark. 6. Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
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.
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 CTNNB1p.T41A mutation in ctDNA and tumor samples from HCCpatients 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 CTNNB1p.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 HCCpatients, 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 HCCpatients. A liquid biopsy approach may be useful in a tailored therapy of HCC.
Authors: Paul A Harris; Robert Taylor; Robert Thielke; Jonathon Payne; Nathaniel Gonzalez; Jose G Conde Journal: J Biomed Inform Date: 2008-09-30 Impact factor: 6.317
Authors: Erin Bresnahan; Pedro Molina-Sánchez; Katherine E Lindblad; Barbara Maier; Marina Ruiz de Galarreta; Daniela Sia; Marc Puigvehi; Verónica Miguela; María Casanova-Acebes; Maxime Dhainaut; Carlos Villacorta-Martin; Aatur D Singhi; Akshata Moghe; Johann von Felden; Lauren Tal Grinspan; Shuang Wang; Alice O Kamphorst; Satdarshan P Monga; Brian D Brown; Augusto Villanueva; Josep M Llovet; Miriam Merad; Amaia Lujambio Journal: Cancer Discov Date: 2019-06-11 Impact factor: 39.397