Identifying the clonal origin of synchronous multifocal tumors in the hepatobiliary and pancreatic system using multi-omic platforms
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Weiqin Jiang1,*, Yongfeng Ding2,*, Yifei Shen3,*, Longjiang Fan3, Linfu Zhou4, Zhi Li5, Yi Zheng1, Peng Zhao1, Lulu Liu1, Zhou Tong1, Weijia Fang1, Weilin Wang6,7,8
1Cancer Biotherapy Center, First Affiliated Hospital, Zhejiang University, China
2Department of Surgical Oncology, First Affiliated Hospital, Zhejiang University, China
3Institute of Bioinformatics & Research Center for Air Pollution and Health, Zhejiang University, China
4Medical Biotechnology Laboratory, Zhejiang University, China
5Department of Radiology, First Affiliated Hospital, Zhejiang University, China
6Key Laboratory of Precision Diagnosis & Treatment for Hepatobiliary & Pancreatic Tumor, First Affiliated Hospital, Zhejiang University, China
7Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University, China
8Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China
*These authors contributed equally to this work
Weilin Wang, email: [email protected]
Weijia Fang, email: [email protected]
Weiqin Jiang, email: [email protected]
Keywords: synchronous multifocal tumors, hepatobiliary and pancreatic system, mutation, copy number variation, single clonal evolution
Received: July 27, 2016 Accepted: December 07, 2016 Published: December 19, 2016
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.
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