Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Clin Cancer Res. 2019 Oct 15;25(20):6107-6118. doi: 10.1158/1078-0432.CCR-18-3341. Epub 2019 Jul 30.
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%). was the common altered gene [>120 alterations (non-unique)] followed by [20-38 alterations (nonunique)/gene]. Of the patients with alterations, 56.9% (103/181) had ≥1 actionable alterations, most commonly in . In these genes, amplifications occurred more frequently than mutations. Hepatitis B (HBV)-positive patients were more likely to have alterations, 35.7% (5/14) versus 8.8% HBV-negative ( = 0.04).
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.
分子谱分析已被用于选择靶向治疗患者和确定预后。鉴于获得肝组织活检的挑战，对于肝细胞癌（HCC），非侵入性策略至关重要。
我们使用循环肿瘤 DNA（ctDNA）的综合基因组检测（Guardant Health）分析了 206 例 HCC 患者的血液样本。
总共 206 例患者中有 153 例（74.3%）为男性；中位年龄为 62 岁（范围为 18-91 岁）。总共 181 例患者有≥1 种改变。总改变数为 680 个（非独特）；中位改变数/患者为三个（范围为 1-13）；中位突变等位基因频率（% cfDNA）为 0.49%（范围为 0.06%-55.03%）。是最常见的改变基因[>120 个改变（非独特）]，其次是 [20-38 个改变（非独特）/基因]。在有改变的患者中，56.9%（103/181）有≥1 种可操作改变，最常见于 。在这些基因中，扩增比突变更常见。HBV 阳性患者更有可能发生 改变，35.7%（5/14）与 HBV 阴性患者（8.8%，=0.04）相比。
本研究代表了美国首例对 HCC 血液源性 ctDNA 的大规模分析。基于 HCC 危险因素的基因组差异和高比例潜在可操作的基因组改变表明该技术具有潜在的临床应用价值。
