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Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The beta-catenin gene, CTNNB1, is among the most frequently mutated in HCC tissues. However, mutational analysis of HCC tumors is hampered by the difficulty of obtaining tissue samples using traditional biopsy. Her...

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Autores principales: Lin, Selena Y., Chang, Ting-Tsung, Steffen, Jamin D., Chen, Sitong, Jain, Surbhi, Song, Wei, Lin, Yih-Jyh, Su, Ying-Hsiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393790/
https://www.ncbi.nlm.nih.gov/pubmed/34441409
http://dx.doi.org/10.3390/diagnostics11081475
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author Lin, Selena Y.
Chang, Ting-Tsung
Steffen, Jamin D.
Chen, Sitong
Jain, Surbhi
Song, Wei
Lin, Yih-Jyh
Su, Ying-Hsiu
author_facet Lin, Selena Y.
Chang, Ting-Tsung
Steffen, Jamin D.
Chen, Sitong
Jain, Surbhi
Song, Wei
Lin, Yih-Jyh
Su, Ying-Hsiu
author_sort Lin, Selena Y.
collection PubMed
description Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The beta-catenin gene, CTNNB1, is among the most frequently mutated in HCC tissues. However, mutational analysis of HCC tumors is hampered by the difficulty of obtaining tissue samples using traditional biopsy. Here, we explored the feasibility of detecting tumor-derived CTNNB1 mutations in cell-free DNA (cfDNA) extracted from the urine of HCC patients. Using a short amplicon qPCR assay targeting HCC mutational hotspot CTNNB1 codons 32–37 (exon 3), we detected CTNNB1 mutations in 25% (18/73) of HCC tissues and 24% (15/62) of pre-operative HCC urine samples in two independent cohorts. Among the CTNNB1-mutation-positive patients with available matched pre- and post-operative urine (n = 13), nine showed apparent elimination (n = 7) or severalfold reduction (n = 2) of the mutation in urine following tumor resection. Four of the seven patients with no detectable mutations in postoperative urine remained recurrence-free within five years after surgery. In contrast, all six patients with mutation-positive in post-operative urine recurred, including the two with reduced mutation levels. This is the first report of association between the presence of CTNNB1 mutations in pre- and post-operative urine cfDNA and HCC recurrence with implications for minimum residual disease detection.
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spelling pubmed-83937902021-08-28 Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients Lin, Selena Y. Chang, Ting-Tsung Steffen, Jamin D. Chen, Sitong Jain, Surbhi Song, Wei Lin, Yih-Jyh Su, Ying-Hsiu Diagnostics (Basel) Article Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. The beta-catenin gene, CTNNB1, is among the most frequently mutated in HCC tissues. However, mutational analysis of HCC tumors is hampered by the difficulty of obtaining tissue samples using traditional biopsy. Here, we explored the feasibility of detecting tumor-derived CTNNB1 mutations in cell-free DNA (cfDNA) extracted from the urine of HCC patients. Using a short amplicon qPCR assay targeting HCC mutational hotspot CTNNB1 codons 32–37 (exon 3), we detected CTNNB1 mutations in 25% (18/73) of HCC tissues and 24% (15/62) of pre-operative HCC urine samples in two independent cohorts. Among the CTNNB1-mutation-positive patients with available matched pre- and post-operative urine (n = 13), nine showed apparent elimination (n = 7) or severalfold reduction (n = 2) of the mutation in urine following tumor resection. Four of the seven patients with no detectable mutations in postoperative urine remained recurrence-free within five years after surgery. In contrast, all six patients with mutation-positive in post-operative urine recurred, including the two with reduced mutation levels. This is the first report of association between the presence of CTNNB1 mutations in pre- and post-operative urine cfDNA and HCC recurrence with implications for minimum residual disease detection. MDPI 2021-08-14 /pmc/articles/PMC8393790/ /pubmed/34441409 http://dx.doi.org/10.3390/diagnostics11081475 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, Selena Y.
Chang, Ting-Tsung
Steffen, Jamin D.
Chen, Sitong
Jain, Surbhi
Song, Wei
Lin, Yih-Jyh
Su, Ying-Hsiu
Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients
title Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients
title_full Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients
title_fullStr Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients
title_full_unstemmed Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients
title_short Detection of CTNNB1 Hotspot Mutations in Cell-Free DNA from the Urine of Hepatocellular Carcinoma Patients
title_sort detection of ctnnb1 hotspot mutations in cell-free dna from the urine of hepatocellular carcinoma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393790/
https://www.ncbi.nlm.nih.gov/pubmed/34441409
http://dx.doi.org/10.3390/diagnostics11081475
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