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 - Funding Information:
Bili Project Foundation, Inc.-UCSF Hepatobiliary Tissue Bank and Registry. This work was supported in part by the NIH through grants CA170035 and CA190945 (to A.O. Kaseb), CA106458 (to M.M. Hassan), and CA178744 (to J. Morris), The Cancer Prevention and Research Institute of Texas RP150535 (to N.S. Sánchez, F. Meric-Bernstam), the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy 1U01 CA180964 (to N.S. Sánchez,
Funding Information:
Bili Project Foundation, Inc.-UCSF Hepatobiliary Tissue Bank and Registry. This work was supported in part by the NIH through grants CA170035 and CA190945 (to A.O. Kaseb), CA106458 (to M.M. Hassan), and CA178744 (to J. Morris), The Cancer Prevention and Research Institute of Texas RP150535 (to N.S. Sanchez, F. Meric-Bernstam), the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy 1U01 CA180964 (to N.S. Sanchez, K.R. Mills-Shaw, F. Meric-Bernstam), NCATS Grant UL1 TR000371 (Center for Clinical and Translational Sciences), and MD Anderson Cancer Center Support Grant (P30 CA016672).
Funding Information:
R.K. Kelley is a consultant/advisory board member for Genentech/Roche and TargetPharma Solutions. K.C. Banks holds ownership interest (including patents) in Guardant Health, Inc. R.B. Lanman is an employee of Guardant Health, Inc.; holds ownership interest (including patents) in Guardant Health, Blolase, and Forward Medical; and is a consultant/ advisory board member for Forward Medical, Inc. A. Talasaz is an employee of and holds ownership interest (including patents) in Guardant Health, Inc. F. Meric-Bernstam reports receiving commercial research grants from Novartis, AstraZeneca, Taiho, Genentech, Calithera, Debio, Bayer, Aileron, PUMA, CytoMx, Zymeworks, Curis, Pfizer, eFFECTOR, Abbvie, Guardant Health, Daiichi Sankyo, and GlaxoSmithKline; reports receiving speakers bureau honoraria from Sumitomo Dainippon Pharma and Dialectica; and is a consultant/advisory board member for Genentech, Inflection Biosciences, Pieris, Darwin Health, Samsung Bioepis, Aduro, Spectrum, Origi-Med, Debio, Xencor, Jackson Laboratory, and Mersana. S. Ikeda reports receiving speakers bureau honoraria from Guardant Health, Chugai Pharmaceutical, and AstraZeneca. R. Kurzrock is an employee of CureMatch, Inc.; reports receiving other commercial research support to her institution from Incyte, Genentech, Merck Serono, Pfizer, Sequenom, Foundation Medicine, Guardant Health, Grifols, Konica Minolta, DeBipharm, Boehringer Ingelheim, and OmniSeq; reports receiving speakers bureau honoraria from Roche; holds ownership interest (including patents) in IDbyDNA, Cure-Match, and Soluventis; and is an unpaid consultant/advisory board member for Gaido, LOXO, X-Biotech, Actuate Therapeutics, Roche, NeoMed, Solu-venits, and Pfizer. No potential conflicts of interest were disclosed by the other authors.
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
UR - http://www.scopus.com/inward/citedby.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 -