Targeted Molecular Profiling of Circulating Cell-Free DNA in Patients With Advanced Hepatocellular Carcinoma.
JCO Precis Oncol
; 7: e2300272, 2023 09.
Article
em En
| MEDLINE
| ID: mdl-37769223
ABSTRACT
PURPOSE:
Next-generation sequencing (NGS) of tumor-derived, circulating cell-free DNA (cfDNA) may aid in diagnosis, prognostication, and treatment of patients with hepatocellular carcinoma (HCC). The operating characteristics of cfDNA mutational profiling must be determined before routine clinical implementation.METHODS:
This was a single-center, retrospective study with the primary objective of defining genomic alterations in circulating cfDNA along with plasma-tissue genotype agreement between NGS of matched tumor samples in patients with advanced HCC. cfDNA was analyzed using a clinically validated 129-gene NGS assay; matched tissue-based NGS was analyzed with a US Food and Drug Administration-authorized NGS tumor assay.RESULTS:
Fifty-three plasma samples from 51 patients with histologically confirmed HCC underwent NGS-based cfDNA analysis. Genomic alterations were detected in 92.2% of patients, with the most commonly mutated genes including TERT promoter (57%), TP53 (47%), CTNNB1 (37%), ARID1A (18%), and TSC2 (14%). In total, 37 (73%) patients underwent paired tumor NGS, and concordance was high for mutations observed in patient-matched plasma samples TERT (83%), TP53 (94%), CTNNB1 (92%), ARID1A (100%), and TSC2 (71%). In 10 (27%) of 37 tumor-plasma samples, alterations were detected by cfDNA analysis that were not detected in the patient-matched tumors. Potentially actionable mutations were identified in 37% of all cases including oncogenic/likely oncogenic alterations in TSC1/2 (18%), BRCA1/2 (8%), and PIK3CA (8%). Higher average variant allele fraction was associated with elevated alpha-fetoprotein, increased tumor volume, and no previous systemic therapy, but did not correlate with overall survival in treatment-naïve patients.CONCLUSION:
Tumor mutation profiling of cfDNA in HCC represents an alternative to tissue-based genomic profiling, given the high degree of tumor-plasma NGS concordance; however, genotyping of both blood and tumor may be required to detect all clinically actionable genomic alterations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Ácidos Nucleicos Livres
/
DNA Tumoral Circulante
/
Neoplasias Hepáticas
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
JCO Precis Oncol
Ano de publicação:
2023
Tipo de documento:
Article