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

Diagnostics

Ting-Tsung Chang¹  Yih-Jyh Lin²  Jamin D. Steffen³  Surbhi Jain³  Selena Y. Lin³  Wei Song³  Sitong Chen³  Ying-Hsiu Su⁴ 

[1] Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;Department of Surgery, National Cheng Kung University Medical College and Hospital, Tainan 701, Taiwan;JBS Science, Inc., Doylestown, PA 18902, USA;The Baruch S. Blumberg Research Institute, Doylestown, PA 18902, USA;

关键词: hepatocellular carcinoma;    cell-free DNA;    beta-catenin;    urine;    mutation;    recurrence;   

DOI  :  10.3390/diagnostics11081475

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown