Somatic mutations in circulating cell-free DNA and risk for hepatocellular carcinoma in hispanics

Jingjing Jiao, Jessica I. Sanchez, Erika J. Thompson, Xizeng Mao, Joseph B. McCormick, Susan P. Fisher-Hoch, P. Andrew Futreal, Jianhua Zhang, Laura Beretta

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 muta-tions. 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.

Original languageEnglish (US)
Article number7411
JournalInternational journal of molecular sciences
Volume22
Issue number14
DOIs
StatePublished - Jul 2 2021

Keywords

  • Disease prevention
  • Health disparities
  • Hepatobiliary diseases
  • Precision medicine

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

MD Anderson CCSG core facilities

  • Advanced Technology Genomics Core

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