Identifying the clonal origin of synchronous multifocal tumors in the hepatobiliary and pancreatic system using multi-omic platforms.
Identifying the clonal origin of synchronous multifocal tumors in the hepatobiliary and pancreatic system using multi-omic platforms.
复制标题
使用多组学平台识别肝胆和胰腺系统中同步多灶性肿瘤的克隆起源。
DOI：
10.18632/oncotarget.14018
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发表时间：
2017-01-17
期刊：
影响因子：
--
通讯作者：
Wang W
中科院分区：
文献类型：
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作者：
Jiang W;Ding Y;Shen Y;Fan L;Zhou L;Li Z;Zheng Y;Zhao P;Liu L;Tong Z;Fang W;Wang W
同步性多灶性肿瘤常常给肿瘤学家带来诊断上的挑战。本研究的目的是使用多组学平台确定肝胆胰系统同步多灶性肿瘤的克隆起源和转移关系。从一名50岁汉族男性患者的三个肿块中提取DNA样本，该患者在诊断时患有胰尾、上胆管和网膜的同步多灶性肿瘤。这些样本的克隆来源使用两个平台进行了测试：390个携带癌症相关可操作突变的关键基因的下一代测序（NGS）和全基因组拷贝数变异（CNV）芯片分析。NGS方法显示高突变一致性，并且病变之间的基因CNV谱相似。使用Affytron芯片进一步研究三个样品的全基因组CNV。使用来自癌症基因组图谱（TCGA）的匹配CNV芯片数据，我们开发了一种计算模型，该模型生成肝细胞癌，胰腺癌和胆管癌的组织特异性CNV签名，以准确识别肿瘤样本的起源。在将患者的CNV芯片数据添加到模型中后，所有三个样品都被聚类到胰腺癌分支中。我们的NGS和CNV芯片分析都表明，临床诊断的同步胰腺癌和胆管癌起源于我们患者胰腺中的相同细胞群。这项研究强调了使用基因组工具来推断同步多灶性肿瘤的起源，这可能有助于提高癌症诊断的准确性。
Synchronous multifocal tumors often pose a diagnostic challenge for oncologists. The purpose of this study was to determine the clonal origin and metastatic relationship of synchronous multifocal tumors in the hepatobiliary and pancreatic system using multi-omic platforms. DNA samples were extracted from three masses harvested from a 50-year-old Han Chinese male patient who suffered from synchronous multifocal tumors in the pancreatic tail, upper biliary duct, and omentum at the time of diagnosis. The clonal origin of these samples was tested using two platforms: next-generation sequencing (NGS) of 390 key genes harboring cancer-relevant actionable mutations and whole-genome copy number variation (CNV) chip analysis. The NGS approach revealed high mutational concordance, and the gene CNV profiles were similar between lesions. Whole-genome CNVs for the three samples were further investigated using an Affymetrix chip. Using matched CNV chip data from The Cancer Genome Atlas (TCGA), we developed a computational model that generated tissue-specific CNV signatures for hepatocellular carcinoma, pancreatic carcinoma, and cholangiocarcinoma to accurately identify the origin of the tumor samples. After adding the patient's CNV chip data to the model, all three samples were clustered into the pancreatic cancer branch. Both our NGS and CNV chip analyses suggested that clinically diagnosed synchronous pancreatic cancer and cholangiocarcinoma originated from the same cell population in the pancreas in our patient. This study highlights the use of genomic tools to infer the origin of synchronous multifocal tumors, which could help to improve the accuracy of cancer diagnosis.