Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Ahmed O KasebRazelle Kurzrock

Abstract

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. We analyzed blood samples from 206 patients with HCC using comprehensive genomic testing (Guardant Health) of circulating tumor DNA (ctDNA). 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). This study represents the first large-sc...Continue Reading

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Citations

Apr 28, 2020·Journal of Cancer Research and Clinical Oncology·Sameer A Dhayat, Zixuan Yang
Jun 24, 2020·International Journal of Cancer. Journal International Du Cancer·Rei OkadaHideaki Shimada
Apr 3, 2020·Clinical and Experimental Medicine·Jialei WengNing Ren
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Jun 3, 2021·Cancers·Filippo PelizzaroFabio Farinati
Jul 25, 2021·International Journal of Molecular Sciences·Jingjing JiaoLaura Beretta
Sep 18, 2021·Hepatology Communications·Nia Adeniji, Renumathy Dhanasekaran

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