https://scholars.lib.ntu.edu.tw/handle/123456789/470461
標題: | Targeted next-generation sequencing identifies distinct clinicopathologic and molecular entities of intraductal papillary neoplasms of the bile duct | 作者: | CHING-YAO YANG Huang, Wei-Ju JIA-HUEI TSAI Cheng, Arkady Chen, Chih-Chi Hsu, Hung-Pin YUNG-MING JENG |
公開日期: | 2019 | 出版社: | Nature Publishing Group | 卷: | 32 | 期: | 11 | 起(迄)頁: | 1637-1645 | 來源出版物: | Modern Pathology | 摘要: | Intraductal papillary neoplasm of the bile duct (IPNB) is a mass-forming neoplasm in the bile duct considered to be the biliary counterpart of pancreatic intraductal papillary mucinous neoplasm (IPMN). By its cell lineage, IPNB can be classified into gastric, intestinal, pancreatobiliary, and oncocytic types. Recently, a group of Japanese and Korean pathologists proposed that IPNB be classified into two types, with type 1, being the histological counterpart of IPMN and type 2, having a more complex histological architecture. We used targeted next-generation sequencing to study the molecular change of 37 IPNBs and identified frequent mutations of KRAS (49%), GNAS (32%), RNF43 (24%), APC (24%), TP53 (24%), and CTNNB1 (11%) in IPNBs. Intestinal-type IPNB was associated with KRAS, GNAS, and RNF43 mutations. Japan–Korea consensus type 1 was associated with KRAS and GNAS mutations. All four IPNBs with CTNNB1 mutations were of pancreatobiliary type and located in the extrahepatic bile duct. A hierarchical analysis identified three distinct groups within IPNB: group 1 was Japan–Korea consensus type 1 tumors with macroscopic mucin, old age, and frequent KRAS, GNAS, and RNF43 mutations. Group 2 was Japan–Korea consensus type 2 with intestinal differentiation and frequent KRAS mutation but rare GNAS mutation, MUC2 expression, and macroscopic mucin. Group 3 was characterized by CTNNB1 mutation, extrahepatic location, lack of expression of intestinal markers, Japan–Korea consensus type 2, and lack of mutations in KRAS, APC, RNF43, and GNAS. Our results indicated that IPNB is a heterogeneous disease and that the activation of Ras-mitogen-activated protein kinase (MAPK), Wnt/β-catenin, and G-protein-coupled receptor (GPCR)–cAMP signaling is the main oncogenic mechanism of IPNB. ? 2019, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068061131&doi=10.1038%2fs41379-019-0306-9&partnerID=40&md5=2a27934fc9ec870d6c7498df5cd0dc2d https://scholars.lib.ntu.edu.tw/handle/123456789/470461 |
ISSN: | 0893-3952 | DOI: | 10.1038/s41379-019-0306-9 | SDG/關鍵字: | APC protein; beta catenin; ctnnb1 protein; G protein coupled receptor; genomic DNA; gnas protein; K ras protein; mitogen activated protein kinase; mucin 1; mucin 2; protein p53; rnf43 protein; unclassified drug; Wnt protein; adult; aged; Article; bile duct tumor; cAMP signaling; carcinogenesis; clinical feature; extrahepatic bile duct; female; gene expression; gene identification; gene mutation; genetic association; histopathology; human; human cell; human tissue; intestine; intraductal papillary neoplasm of the bile duct; intrahepatic bile duct; male; MAPK signaling; next generation sequencing; priority journal; tumor differentiation; Wnt signaling; bile duct cancer; genetics; high throughput sequencing; middle aged; mutation; Paget nipple disease; papillary carcinoma; pathology; physiology; signal transduction; very elderly; Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Carcinoma, Ductal; Carcinoma, Papillary; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Middle Aged; Mutation; Signal Transduction |
顯示於: | 病理學科所 |
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