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

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 fibrosi...

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Autores principales: Jiao, Jingjing, Sanchez, Jessica I., Thompson, Erika J., Mao, Xizeng, McCormick, Joseph B., Fisher-Hoch, Susan P., Futreal, P. Andrew, Zhang, Jianhua, Beretta, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304329/
https://www.ncbi.nlm.nih.gov/pubmed/34299031
http://dx.doi.org/10.3390/ijms22147411
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author Jiao, Jingjing
Sanchez, Jessica I.
Thompson, Erika J.
Mao, Xizeng
McCormick, Joseph B.
Fisher-Hoch, Susan P.
Futreal, P. Andrew
Zhang, Jianhua
Beretta, Laura
author_facet Jiao, Jingjing
Sanchez, Jessica I.
Thompson, Erika J.
Mao, Xizeng
McCormick, Joseph B.
Fisher-Hoch, Susan P.
Futreal, P. Andrew
Zhang, Jianhua
Beretta, Laura
author_sort Jiao, Jingjing
collection PubMed
description 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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spelling pubmed-83043292021-07-25 Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics Jiao, Jingjing Sanchez, Jessica I. Thompson, Erika J. Mao, Xizeng McCormick, Joseph B. Fisher-Hoch, Susan P. Futreal, P. Andrew Zhang, Jianhua Beretta, Laura Int J Mol Sci Article 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. MDPI 2021-07-10 /pmc/articles/PMC8304329/ /pubmed/34299031 http://dx.doi.org/10.3390/ijms22147411 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jiao, Jingjing
Sanchez, Jessica I.
Thompson, Erika J.
Mao, Xizeng
McCormick, Joseph B.
Fisher-Hoch, Susan P.
Futreal, P. Andrew
Zhang, Jianhua
Beretta, Laura
Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics
title Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics
title_full Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics
title_fullStr Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics
title_full_unstemmed Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics
title_short Somatic Mutations in Circulating Cell-Free DNA and Risk for Hepatocellular Carcinoma in Hispanics
title_sort somatic mutations in circulating cell-free dna and risk for hepatocellular carcinoma in hispanics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304329/
https://www.ncbi.nlm.nih.gov/pubmed/34299031
http://dx.doi.org/10.3390/ijms22147411
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