We aimed to assess the utility of a novel, noninvasive method of detecting genomic alterations in patients with gastrointestinal malignancies, i.e., the use of liquid biopsies to obtain blood-derived circulating tumor DNA (ctDNA) through an analysis of the genomic landscape of ctDNA (68 genes) from 213 patients with advanced gastrointestinal cancers. The most common cancer types were colorectal adenocarcinoma (N = 55; 26%), appendiceal adenocarcinoma (N = 46; 22%), hepatocellular carcinoma (N = 31; 15%), and pancreatic ductal adenocarcinoma (N = 25; 12%). The majority of patients (58%) had ≥1 characterized alteration (excluded variants of unknown significance). The median number of characterized alterations was 1 (range, 0–13). The number of detected alterations per patient varied between different cancer types: in hepatocellular carcinoma, 74% of patients (23/31) had ≥1 characterized alteration(s) versus 24% of appendiceal adenocarcinoma patients (11/46). The median percent ctDNA among characterized alterations was 2.50% (interquartile range, 0.76%–8.96%). Overall, 95% of patients (117/123) had distinct molecular portfolios with 143 unique characterized alterations within 56 genes. Overall, concordance rates of 96%, 94%, 95%, and 91%, respectively, were found between ctDNA and tissue biopsy (N = 105 patients) in the four most common alterations (KRAS amplification, MYC amplification, KRAS G12V, and EGFR amplification). Of 123 patients with characterized alterations, >99% (122/123; 57% of entire population tested; 122/213) had one or more alterations potentially actionable by experimental or approved drugs. These observations suggest that many patients with gastrointestinal tumors, including difficult-to-biopsy malignancies like hepatocellular cancers, frequently have discernible and theoretically pharmacologically tractable ctDNA alterations that merit further studies in prospective trials. Mol Cancer Ther; 17(1); 297–305. ©2017 AACR.

中文翻译：

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循环肿瘤 DNA 反映的胃肠道恶性肿瘤的突变景观

我们的目的是评估一种检测胃肠道恶性肿瘤患者基因组改变的新型非侵入性方法的实用性，即使用液体活检通过分析 ctDNA 的基因组图谱来获取血液来源的循环肿瘤 DNA (ctDNA)。 68 个基因）来自 213 名晚期胃肠癌患者。最常见的癌症类型是结直肠腺癌（N = 55；26%）、阑尾腺癌（N = 46；22%）、肝细胞癌（N = 31；15%）和胰腺导管腺癌（N = 25；12%） ）。大多数患者 (58%) 具有 ≥1 个特征性改变（排除意义不明的变异）。特征改变的中位数为 1（范围：0-13）。每个患者检测到的改变数量因癌症类型而异：在肝细胞癌中，74% 的患者 (23/31) 具有 ≥1 个特征性改变，而阑尾腺癌患者中这一比例为 24% (11/46)。特征性改变中 ctDNA 的中位百分比为 2.50%（四分位数范围，0.76%–8.96%）。总体而言，95% 的患者 (117/123) 具有不同的分子组合，其中 56 个基因内有 143 个独特的特征改变。总体而言，ctDNA 和组织活检（N = 105 名患者）在四种最常见的改变（KRAS 扩增、MYC 扩增、KRAS G12V 和EGFR 扩增）。在 123 名具有特征性改变的患者中，>99%（122/123；受测试的整个人群的 57%；122/213）具有一种或多种可能可以通过实验或批准的药物进行治疗的改变。这些观察结果表明，许多胃肠道肿瘤患者，包括肝细胞癌等难以活检的恶性肿瘤，经常具有可辨别且理论上药理学上可处理的 ctDNA 改变，值得在前瞻性试验中进一步研究。摩尔癌症治疗；17(1)；297–305。©2017 AACR。