Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA.
Molecular Profiling of Hepatocellular Carcinoma Using Circulating Cell-Free DNA.
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DOI：
10.1158/1078-0432.ccr-18-3341
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发表时间：
2019-10-15
影响因子：
11.5
通讯作者：
Kurzrock, Razelle
中科院分区：
文献类型：
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作者：
Kaseb, Ahmed O.;Sanchez, 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 P. S.;Wolff, Robert A.;Yao, James C.;Meric-Bernstam, Funda;Ikeda, Sadakatsu;Kurzrock, Razelle
分子谱分析已被用于选择患者进行靶向治疗和确定预后。鉴于获得肝组织活检的挑战，非侵入性策略对肝细胞癌（HCC）至关重要。我们使用循环肿瘤DNA （ctDNA）的全面基因组检测（Guardant Health， CA）分析了206例HCC患者的血液样本。153/206例（74.3%）为男性；中位年龄62岁（范围18-91岁）。181/206例患者有≥1个改变。修改总数为680个（非唯一）；每位患者中位改变数为3（范围1-13）；中位突变等位基因频率（% cfDNA）为0.49%（范围0.06 ~ 55.03%）。TP53是常见的改变基因（bbb120改变（非唯一）），其次是EGFR、MET、ARID1A、MYC、NF1、BRAF和ERBB2（20-38改变（非唯一）/基因）。在有改变的患者中，56.9%（103/181）有≥1个可操作的改变，最常见的是MYC、EGFR、ERBB2、BRAF、CCNE1、MET、PIK3CA、ARID1A、CDK6和KRAS。在这些基因中，扩增比突变发生得更频繁。乙型肝炎（HBV）阳性患者更容易发生ERBB2改变，为35.7%(5/14)，而HBV阴性患者为8.8% （p=0.04）。这项研究代表了美国HCC中血液来源的ctDNA的第一次大规模分析。基于HCC危险因素的基因组区分和潜在可操作的基因组改变的高比例表明该技术具有潜在的临床应用价值。
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 HCC patients using comprehensive genomic testing (Guardant Health, CA) of circulating tumor DNA (ctDNA). 153/206 (74.3%) were men; median age, 62 years (range, 18–91 years). 181/206 patients had ≥1 alteration. The total number of alterations was 680 (non-unique); median number of alterations/patient was 3 (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 (non-unique)/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-scale analysis of blood-derived ctDNA in HCC in USA. The genomic distinction based on HCC risk factors and the high percentage of potentially actionable genomic alterations suggests potential clinical utility for this technology.