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Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA
- Kaseb, Ahmed O;
- Sánchez, Nora S;
- Sen, Shiraj;
- Kelley, Robin K;
- Tan, Benjamin;
- Bocobo, Andrea G;
- Lim, Kian H;
- Abdel-Wahab, Reham;
- Uemura, Marc;
- Pestana, Roberto Carmagnani;
- Qiao, Wei;
- Xiao, Lianchun;
- Morris, Jeffrey;
- Amin, Hesham M;
- Hassan, Manal M;
- Rashid, Asif;
- Banks, Kimberly C;
- Lanman, Richard B;
- Talasaz, AmirAli;
- Mills-Shaw, Kenna R;
- George, Bhawana;
- Haque, Abedul;
- Raghav, Kanwal PS;
- Wolff, Robert A;
- Yao, James C;
- Meric-Bernstam, Funda;
- Ikeda, Sadakatsu;
- Kurzrock, Razelle
- et al.
Published Web Location
https://doi.org/10.1158/1078-0432.ccr-18-3341Abstract
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.
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