title: Identifying the clonal origin of synchronous multifocal tumors in the hepatobiliary and pancreatic system using multi-omic platforms.
abstract: 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.
authors.affiliation: Cancer Biotherapy Center, First Affiliated Hospital, Zhejiang University, China.
authors.forename: Weiqin
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Surgical Oncology, First Affiliated Hospital, Zhejiang University, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Institute of Bioinformatics & Research Center for Air Pollution and Health, Zhejiang University, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Institute of Bioinformatics & Research Center for Air Pollution and Health, Zhejiang University, China.
authors.forename: Longjiang
authors.initials: L
authors.lastname: Fan
authors.affiliation: Medical Biotechnology Laboratory, Zhejiang University, China.
authors.forename: Linfu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Radiology, First Affiliated Hospital, Zhejiang University, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Cancer Biotherapy Center, First Affiliated Hospital, Zhejiang University, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Cancer Biotherapy Center, First Affiliated Hospital, Zhejiang University, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Cancer Biotherapy Center, First Affiliated Hospital, Zhejiang University, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cancer Biotherapy Center, First Affiliated Hospital, Zhejiang University, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Cancer Biotherapy Center, First Affiliated Hospital, Zhejiang University, China.
authors.forename: Weijia
authors.initials: W
authors.lastname: Fang
authors.affiliation: Key Laboratory of Precision Diagnosis & Treatment for Hepatobiliary & Pancreatic Tumor, First Affiliated Hospital, Zhejiang University, China.|Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
mesh_terms: D001650:Bile Duct Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000235:genetics; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000000981:diagnostic imaging / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics*; D017422:Sequence Analysis, DNA
keywords: copy number variation; hepatobiliary and pancreatic system; mutation; single clonal evolution; synchronous multifocal tumors