Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics.

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.