Targeted Molecular Profiling of Circulating Cell-Free DNA in Patients With Advanced Hepatocellular Carcinoma.

Autor:	Cowzer D; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., White JB; Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Chou JF; Weill Medical College of Cornell University, New York, NY.; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY., Chen PJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Kim TH; Weill Medical College of Cornell University, New York, NY.; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY., Khalil DN; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Weill Medical College of Cornell University, New York, NY., El Dika IH; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Weill Medical College of Cornell University, New York, NY., Columna K; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Yaqubie A; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Light JS; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Shia J; Weill Medical College of Cornell University, New York, NY.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY., Yarmohammadi H; Weill Medical College of Cornell University, New York, NY.; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY., Erinjeri JP; Weill Medical College of Cornell University, New York, NY.; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY., Wei AC; Weill Medical College of Cornell University, New York, NY.; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Jarnagin W; Weill Medical College of Cornell University, New York, NY.; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY., Do RKG; Weill Medical College of Cornell University, New York, NY.; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY., Solit DB; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; Weill Medical College of Cornell University, New York, NY., Capanu M; Weill Medical College of Cornell University, New York, NY.; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY., Shah RH; Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY., Berger MF; Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.; Weill Medical College of Cornell University, New York, NY., Abou-Alfa GK; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Weill Medical College of Cornell University, New York, NY., Harding JJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.; Weill Medical College of Cornell University, New York, NY.
Jazyk:	angličtina
Zdroj:	JCO precision oncology [JCO Precis Oncol] 2023 Sep; Vol. 7, pp. e2300272.
DOI:	10.1200/PO.23.00272
Abstrakt:	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.
Databáze:	MEDLINE
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