Circumventing intratumoral heterogeneity to identify potential therapeutic targets in hepatocellular carcinoma
Circumventing intratumoral heterogeneity to identify potential therapeutic targets in hepatocellular carcinoma
复制标题
规避瘤内异质性以确定肝细胞癌的潜在治疗靶点
DOI：
10.1016/j.jhep.2017.03.005
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发表时间：
2017-08-01
影响因子：
25.7
通讯作者：
Zhou, Jian
中科院分区：
文献类型：
--
作者：
Huang, Ao;Zhao, Xin;Zhou, Jian
背景与目的：由于肿瘤内的异质性，在肝细胞癌中识别靶基因突变用于治疗是具有挑战性的。与单个肿瘤样本相比，循环中的无细胞DNA(CfDNA)可能包含更完整的突变谱。方法：对5例患者32例多区域肿瘤标本进行全外显子测序(WES)和靶向深度测序(TDS)。对匹配的术前cfDNA进行相应的测序。使用非普遍存在的突变(存在于部分肿瘤区域)的平均百分比来衡量肿瘤内的异质性。比较单个肿瘤标本和cfDNA的图谱效率。结果：观察到不同程度的异质性，具有分支和平行的进化模式。TDS测序深度越高，异质性越低(28.1%比34.9%，P
Background & Aims: Identifying target genetic mutations in hepatocellular carcinoma (HCC) for therapy is made challenging by intratumoral heterogeneity. Circulating cell-free DNAs (cfDNA) may contain a more complete mutational spectrum compared to a single tumor sample. This study aimed to identify the most efficient strategy to identify all the mutations within heterogeneous HCCs.Methods: Whole exome sequencing (WES) and targeted deep sequencing (TDS) were carried out in 32 multi-regional tumor samples from five patients. Matched preoperative cfDNAs were sequenced accordingly. Intratumoral heterogeneity was measured using the average percentage of non-ubiquitous mutations (present in parts of tumor regions). Profiling efficiencies of single tumor specimen and cfDNA were compared. The strategy with the highest performance was used to screen for actionable mutations.Results: Variable levels of heterogeneity with branched and parallel evolution patterns were observed. The heterogeneity decreased at higher sequencing depth of TDS compared to measurements by WES (28.1% vs. 34.9%, p