TY - JOUR
T1 - Molecular profiling of hepatocellular carcinoma using circulating cell-free DNA
AU - Kaseb, Ahmed O.
AU - Sanchez, Nora S.
AU - Sen, Shiraj
AU - Kelley, Robin K.
AU - Tan, Benjamin
AU - Bocobo, Andrea G.
AU - Lim, Kian H.
AU - Abdel-Wahab, Reham
AU - Uemura, Marc
AU - Pestana, Roberto Carmagnani
AU - Qiao, Wei
AU - Xiao, Lianchun
AU - Morris, Jeffrey
AU - Amin, Hesham M.
AU - Hassan, Manal M.
AU - Rashid, Asif
AU - Banks, Kimberly C.
AU - Lanman, Richard B.
AU - Talasaz, Amir Ali
AU - Mills-Shaw, Kenna R.
AU - George, Bhawana
AU - Haque, Abedul
AU - Raghav, Kanwal P.S.
AU - Wolff, Robert A.
AU - Yao, James C.
AU - Meric-Bernstam, Funda
AU - Ikeda, Sadakatsu
AU - Kurzrock, Razelle
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/10/15
Y1 - 2019/10/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85072574769&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-18-3341
DO - 10.1158/1078-0432.CCR-18-3341
M3 - Article
C2 - 31363003
AN - SCOPUS:85072574769
SN - 1078-0432
VL - 25
SP - 6107
EP - 6118
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 20
ER -