https://scholars.lib.ntu.edu.tw/handle/123456789/585862
標題: | RNF43 mutation frequently occurs with GNAS mutation and mucin hypersecretion in intraductal papillary neoplasms of the bile duct | 作者: | JIA-HUEI TSAI JAU-YU LIAU CHANG-TSU YUAN Cheng M.-L. RAY-HWANG YUAN YUNG-MING JENG |
公開日期: | 2017 | 出版社: | Blackwell Publishing Ltd | 卷: | 70 | 期: | 5 | 起(迄)頁: | 756-765 | 來源出版物: | Histopathology | 摘要: | Aims: RNF43 is a tumour suppressor gene that suppresses the Wnt–β-catenin signalling pathway. We investigated the role of RNF43 in intraductal papillary neoplasm of the bile duct (IPNB). Methods and results: We conducted mutation analysis of RNF43 in 50 IPNBs, and identified six (12%) RNF43 mutations. RNF43 mutation was more frequent in the intestinal subtype of IPNB (17%) than in the gastric/pancreatobiliary subtype (5%). There was a strong association of RNF43 mutation with GNAS (P = 0.007) mutation, and a borderline correlation with KRAS (P = 0.074) mutation. The presence of macroscopic mucin hypersecretion was closely related to RNF43 (P = 0.024) and GNAS (P < 0.001) mutations. A two-step clustering analysis algorithm successfully categorized IPNBs into two subgroups by using the clinicopathological and molecular features of IPNBs. One subgroup of IPNB represented the ‘biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas’ (biliary-IPMN), and showed unique features reminiscent of IPMN, such as macroscopic and microscopic mucin hypersecretion, an intestinal cell lineage, GNAS mutation, and RNF43 mutation. Biliary-IPMNs were significantly associated with high expression of cytokeratin (CK) 20, mucin 2 (MUC2), and CDX2, as shown by immunostaining (P = 0.032, P = 0.001, and P = 0.026, respectively), and had a borderline association with low expression of CK7 (P = 0.063). With the use of this splitting algorithm, RNF43 mutations were identified in 36% of the biliary-IPMNs. Conclusions: The identification of RNF43 mutations in a distinct subset of IPNBs revealed a new molecular role in the pathogenesis of IPNB, and provided a potential application for cancer therapeutics by the use of Wnt pathway inhibitors. ? 2016 John Wiley & Sons Ltd |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85010750308&doi=10.1111%2fhis.13125&partnerID=40&md5=920792d6eefb29c7419482b43b3c5463 https://scholars.lib.ntu.edu.tw/handle/123456789/585862 |
ISSN: | 0309-0167 | DOI: | 10.1111/his.13125 | SDG/關鍵字: | cytokeratin 20; GNAS protein; K ras protein; mucin; RING finger protein; Ring finger protein 43; transcription factor Cdx2; tumor suppressor protein; unclassified drug; chromogranin; DNA binding protein; GNAS protein, human; mucin; oncoprotein; RNF43 protein, human; stimulatory guanine nucleotide binding protein; aged; Article; bile duct cancer; female; gene mutation; human; human tissue; immunohistochemistry; intraductal papillary mucinous tumor; intraductal papillary neoplasm of the bile duct; male; mutational analysis; priority journal; protein expression; protein secretion; adult; algorithm; bile duct tumor; cluster analysis; dna mutational analysis; genetics; middle aged; mutation; Paget nipple disease; papillary carcinoma; pathology; polymerase chain reaction; secretion (process); very elderly; Adult; Aged; Aged, 80 and over; Algorithms; Bile Duct Neoplasms; Carcinoma, Ductal; Carcinoma, Papillary; Chromogranins; Cluster Analysis; DNA Mutational Analysis; DNA-Binding Proteins; Female; GTP-Binding Protein alpha Subunits, Gs; Humans; Immunohistochemistry; Male; Middle Aged; Mucins; Mutation; Oncogene Proteins; Polymerase Chain Reaction |
顯示於: | 醫學院附設癌醫中心醫院(臺大癌醫) |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。