Faculty Collaboration Database

Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA. Clin Cancer Res 2019 Oct 15;25(20):6107-6118

Date

08/01/2019

Pubmed ID

31363003

Pubmed Central ID

PMC9292132

DOI

10.1158/1078-0432.CCR-18-3341

Scopus ID

2-s2.0-85072574769 (requires institutional sign-in at Scopus site)   52 Citations

Abstract

PURPOSE: Molecular profiling has been used to select patients for targeted therapy and determine prognosis. Noninvasive strategies are critical to hepatocellular carcinoma (HCC) given the challenge of obtaining liver tissue biopsies.

EXPERIMENTAL DESIGN: We analyzed blood samples from 206 patients with HCC using comprehensive genomic testing (Guardant Health) of circulating tumor DNA (ctDNA).

RESULTS: A total of 153/206 (74.3%) were men; median age, 62 years (range, 18-91 years). A total of 181/206 patients had ≥1 alteration. The total number of alterations was 680 (nonunique); median number of alterations/patient was three (range, 1-13); median mutant allele frequency (% cfDNA), 0.49% (range, 0.06%-55.03%). TP53 was the common altered gene [>120 alterations (non-unique)] followed by EGFR, MET, ARID1A, MYC, NF1, BRAF, and ERBB2 [20-38 alterations (nonunique)/gene]. Of the patients with alterations, 56.9% (103/181) had ≥1 actionable alterations, most commonly in MYC, EGFR, ERBB2, BRAF, CCNE1, MET, PIK3CA, ARID1A, CDK6, and KRAS. In these genes, amplifications occurred more frequently than mutations. Hepatitis B (HBV)-positive patients were more likely to have ERBB2 alterations, 35.7% (5/14) versus 8.8% HBV-negative (P = 0.04).

CONCLUSIONS: This study represents the first large-scale analysis of blood-derived ctDNA in HCC in United States. The genomic distinction based on HCC risk factors and the high percentage of potentially actionable genomic alterations suggests potential clinical utility for this technology.

Author List

Kaseb AO, Sánchez NS, Sen S, Kelley RK, Tan B, Bocobo AG, Lim KH, Abdel-Wahab R, Uemura M, Pestana RC, Qiao W, Xiao L, Morris J, Amin HM, Hassan MM, Rashid A, Banks KC, Lanman RB, Talasaz A, Mills-Shaw KR, George B, Haque A, Raghav KPS, Wolff RA, Yao JC, Meric-Bernstam F, Ikeda S, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
Carcinoma, Hepatocellular
Circulating Tumor DNA
Clinical Decision-Making
Cohort Studies
DNA Mutational Analysis
Female
Gene Frequency
Genetic Testing
High-Throughput Nucleotide Sequencing
Humans
Liver Neoplasms
Male
Middle Aged
Mutation
Patient Selection
Prognosis
United States
Young Adult