Synapse - Targeted molecular profiling of circulating cell-free DNA in patients with advanced hepatocellular carcinoma

Targeted molecular profiling of circulating cell-free DNA in patients with advanced hepatocellular carcinoma Journal Article

Authors:	Cowzer, D.; White, J. B.; Chou, J. F.; Chen, P. J.; Kim, T. H.; Khalil, D. N.; El Dika, I. H.; Columna, K.; Yaqubie, A.; Light, J. S.; Shia, J.; Yarmohammadi, H.; Erinjeri, J. P.; Wei, A. C.; Jarnagin, W.; Do, R. K. G.; Solit, D. B.; Capanu, M.; Shah, R. H.; Berger, M. F.; Abou-Alfa, G. K.; Harding, J. J.
Article Title:	Targeted molecular profiling of circulating cell-free DNA in patients with advanced hepatocellular carcinoma
Abstract:	PURPOSENext-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.METHODSThis 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.RESULTSFifty-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-naive patients.CONCLUSIONTumor 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.
Keywords:	biomarker; liquid; tissue; mutations; heterogeneity; biopsies; genomic alterations; tumor dna
Journal Title:	JCO Precision Oncology
Volume:	7
ISSN:	2473-4284
Publisher:	American Society of Clinical Oncology
Date Published:	2023-09-01
Start Page:	e2300272
Language:	English
ACCESSION:	WOS:001174790900001
DOI:	10.1200/po.23.00272
PROVIDER:	wos
PMCID:	PMC10581608
PUBMED:	37769223
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK author is James J. Harding -- Source: Wos