Molecular profiling of hepatocellular carcinoma using circulating cell-free DNA

Ahmed O. Kaseb, Nora S. Sanchez, Shiraj Sen, Robin K. Kelley, Benjamin Tan, Andrea G. Bocobo, Kian H. Lim, Reham Abdel-Wahab, Marc Uemura, Roberto Carmagnani Pestana, Wei Qiao, Lianchun Xiao, Jeffrey Morris, Hesham M. Amin, Manal M. Hassan, Asif Rashid, Kimberly C. Banks, Richard B. Lanman, Amir Ali Talasaz, Kenna R. Mills-ShawBhawana George, Abedul Haque, Kanwal P.S. Raghav, Robert A. Wolff, James C. Yao, Funda Meric-Bernstam, Sadakatsu Ikeda, Razelle Kurzrock

Research output: Contribution to journalArticlepeer-review

41 Scopus 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 (nonunique)] 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 ¼ 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.

Original languageEnglish
Pages (from-to)6107-6118
Number of pages12
JournalClinical Cancer Research
Volume25
Issue number20
DOIs
StatePublished - Oct 15 2019

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