Identifying the clonal origin of synchronous multifocal tumors in the hepatobiliary and pancreatic system using multi-omic platforms.
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.
['Jiang|Weiqin|W|', 'Ding|Yongfeng|Y|', 'Shen|Yifei|Y|', 'Fan|Longjiang|L|', 'Zhou|Linfu|L|', 'Li|Zhi|Z|', 'Zheng|Yi|Y|', 'Zhao|Peng|P|', 'Liu|Lulu|L|', 'Tong|Zhou|Z|', 'Fang|Weijia|W|', 'Wang|Weilin|W|']
D001650:Bile Duct Neoplasms D006528:Carcinoma, Hepatocellular D018281:Cholangiocarcinoma D019295:Computational Biology D056915:DNA Copy Number Variations D023281:Genomics D059014:High-Throughput Nucleotide Sequencing D006801:Humans D008113:Liver Neoplasms D008297:Male D008875:Middle Aged D009154:Mutation D009378:Neoplasms, Multiple Primary D010190:Pancreatic Neoplasms D017422:Sequence Analysis, DNA
synchronous multifocal tumors hepatobiliary and pancreatic system mutation copy number variation single clonal evolution