肝细胞癌
一致性
ARID1A型
PDGFRA公司
靶向治疗
癌症研究
液体活检
胎儿游离DNA
癌
肿瘤科
基因
内科学
医学
病理
突变
生物
癌症
遗传学
间质细胞
产前诊断
怀孕
胎儿
主旨
作者
Darren Cowzer,Jessica White,Joanne F. Chou,Pin‐Jung Chen,Tae-Hyung Kim,Danny N. Khalil,Imane H. El Dika,Katrina Columna,Amin Yaqubie,Joseph S. Light,Jinru Shia,Hooman Yarmohammadi,Joseph P. Erinjeri,Alice C. Wei,William R. Jarnagin,Richard Kinh Gian,David B. Solit,Marinela Capanu,Ronak Shah,Michael F. Berger,Ghassan K. Abou‐Alfa,James J. Harding
出处
期刊:JCO precision oncology
[American Society of Clinical Oncology]
日期:2023-09-01
卷期号: (7)
摘要
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.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.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.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.