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Updated: Oct 27, 2025
Characterizing Mutational Load and Clonal Composition of Human Blood
Published on: July 11, 2019
Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics
Jingjing Jiao1, Jessica I Sanchez1, Erika J Thompson2
1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Insights
Plasma cell-free DNA (cfDNA) mutations can predict hepatocellular carcinoma (HCC) risk and survival in Hispanics. Detecting cfDNA mutations may offer a non-invasive approach for early detection and prognosis in liver disease.
Area of Science:
- Genetics
- Oncology
- Hepatology
Background:
- Hispanics experience a disproportionate burden of liver fibrosis and hepatocellular carcinoma (HCC).
- Advanced liver fibrosis is a significant precursor to HCC development.
- Identifying molecular markers for early detection and prognosis is crucial for this demographic.
Purpose of the Study:
- To identify somatic mutations in cell-free DNA (cfDNA) from plasma samples.
- To compare cfDNA mutation profiles in Hispanics with HCC versus those with advanced liver fibrosis but no HCC.
- To evaluate the correlation between cfDNA features and patient survival outcomes.
Main Methods:
- Targeted sequencing of over 262 cancer-associated genes was performed on plasma cfDNA.
- Mutational analysis was conducted on 27 HCC patients and 51 subjects with advanced liver fibrosis.
- cfDNA concentrations and mutation counts were analyzed in relation to survival.
Main Results:
- Nonsynonymous mutations were detected in 22/27 HCC patients and 17/51 subjects with advanced fibrosis.
- Commonly mutated genes in HCC included CTNNB1, TP53, NFE2L2, and ARID1A; KMT2C was frequent in fibrosis.
- Higher cfDNA concentrations and mutation counts correlated with shorter overall survival in HCC patients and increased mortality risk in fibrosis patients.
Conclusions:
- cfDNA mutations are prevalent in Hispanics with HCC and advanced liver fibrosis.
- cfDNA characteristics show promise as non-invasive biomarkers for HCC risk stratification.
- Plasma cfDNA analysis may aid in predicting overall survival for patients with liver disease.
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.
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