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Clin Cancer Res. 2019 Oct 15;25(20):6107-6118. doi: 10.1158/1078-0432.CCR-18-3341. Epub 2019 Jul 30.

Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA.

Author information

1
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. akaseb@mdanderson.org rkurzrock@ucsd.edu.
2
Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
3
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.
5
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
6
Department of Radiology, Washington University School of Medicine, St. Louis, Missouri.
7
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
8
Arizona Clinical Oncology Department, Assiut University Hospital, Assiut, Egypt.
9
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
10
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
11
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
12
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
13
Guardant Health, Inc., Redwood City, California.
14
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
15
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego, Moores Cancer Center, La Jolla, California.
16
Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California San Diego, Moores Cancer Center, La Jolla, California. akaseb@mdanderson.org rkurzrock@ucsd.edu.

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.

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