Huang Ao, Wang Yu-Peng, Wang Jian, Fu Pei-Yao, Zhang Xin, Cao Ya, Fan Jia, Yang Xin-Rong, Zhou Jian
Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Ministry of Education, Shanghai 200032, China.
Cancer Research Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Central South University, Ministry of Education, Changsha 410078, China.
J Gastrointest Oncol. 2020 Feb;11(1):112-120. doi: 10.21037/jgo.2019.09.13.
Utilization of next-generation sequencing (NGS) to identify potential therapeutic targets and then prescribe matched agents provides new hope for patients with advanced cancer, such as hepatocellular carcinoma (HCC). However, intratumoral heterogeneity (ITH) challenges precise genomic profiling and may lead to target treatment failure. This study aims to evaluate whether and to what extent would genetic profiling be biased by ITH in HCC. We datamined publications focusing on the ITH of HCC and extracted the sequencing and clinicopathological information to make data reanalysis. Potential therapeutic targets and driver genes in HCC were specially pooled as reference to analyze the bias effect of ITH on genetic profiling. Five studies which analyzed ITH using NGS of multi-site samples were enrolled, with a total of 207 tumor samples from 36 HCC patients. The ITH ranged from 5.21% to 88.27% and no correlations between ITH extent and sample numbers, sequencing depth, or clinicopathological parameters were observed. In total, 72 therapeutic and 15 candidate driver genes were pooled as reference. Totally, 38.8% HCCs were found to be drugable in single-site sample, of which only 19.4% might be biased by ITH. Of the driver genes, 86% could be detected in single-site sample. HCC is a highly heterogeneous disease. While ITH indeed hinders comprehensive and precise HCC genome profiling, it has limited influences on identification of actionable and driver mutations. Single-site sampling/biopsy assayed with targeted deep sequencing might be efficient in the clinical management of HCC.
利用下一代测序（NGS）来识别潜在的治疗靶点并随后开具匹配的药物，为晚期癌症患者（如肝细胞癌（HCC））带来了新希望。然而，肿瘤内异质性（ITH）对精确的基因组分析提出了挑战，并可能导致靶向治疗失败。本研究旨在评估ITH在HCC中对基因分析产生偏差的程度。我们挖掘了关注HCC的ITH的文献，并提取测序和临床病理信息进行数据重新分析。特别汇总了HCC中的潜在治疗靶点和驱动基因作为参考，以分析ITH对基因分析的偏差效应。纳入了五项使用多部位样本的NGS分析ITH的研究，共来自36例HCC患者的207个肿瘤样本。ITH范围为5.21%至88.27%，未观察到ITH程度与样本数量、测序深度或临床病理参数之间的相关性。总共汇总了72个治疗基因和15个候选驱动基因作为参考。总体而言，在单部位样本中发现38.8%的HCC具有可用药性，其中只有19.4%可能受ITH影响。在驱动基因中，86%可在单部位样本中检测到。HCC是一种高度异质性疾病。虽然ITH确实阻碍了对HCC基因组的全面精确分析，但它对可操作突变和驱动突变的识别影响有限。采用靶向深度测序的单部位采样/活检在HCC的临床管理中可能是有效的。
