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- Title
Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics.
- Authors
Jiao, Jingjing; Sanchez, Jessica I.; Thompson, Erika J.; Mao, Xizeng; McCormick, Joseph B.; Fisher-Hoch, Susan P.; Futreal, P. Andrew; Zhang, Jianhua; Beretta, Laura
- Abstract
Hispanics are disproportionally affected by liver fibrosis and hepatocellular carcinoma (HCC). Advanced liver fibrosis is a major risk factor for HCC development. We aimed at identifying somatic mutations in plasma cell-free DNA (cfDNA) of Hispanics with HCC and Hispanics with advanced liver fibrosis but no HCC. Targeted sequencing of over 262 cancer-associated genes identified nonsynonymous mutations in 22 of the 27 HCC patients. Mutations were detected in known HCC-associated genes (e.g., CTNNB1, TP53, NFE2L2, and ARID1A). No difference in cfDNA concentrations was observed between patients with mutations and those without detectable mutations. HCC patients with higher cfDNA concentrations or higher number of mutations had a shorter overall survival (p < 0.001 and p = 0.045). Nonsynonymous mutations were also identified in 17 of the 51 subjects with advanced liver fibrosis. KMT2C was the most commonly mutated gene. Nine genes were mutated in both subjects with advanced fibrosis and HCC patients. Again, no significant difference in cfDNA concentrations was observed between subjects with mutations and those without detectable mutations. Furthermore, higher cfDNA concentrations and higher number of mutations correlated with a death outcome in subjects with advanced fibrosis. In conclusion, cfDNA features are promising non-invasive markers for HCC risk prediction and overall survival.
- Subjects
CELL-free DNA; GENETIC mutation; CIRCULATING tumor DNA; SOMATIC mutation; HEPATOCELLULAR carcinoma; OVERALL survival
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 14, p7411
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms22147411