Telomere length of gallbladder epithelium is shortened in patients with congenital biliary dilatation: measurement by quantitative fluorescence in situ hybridization
Telomere length of gallbladder epithelium is shortened in patients with congenital biliary dilatation: measurement by quantitative fluorescence in situ hybridization
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先天性胆道扩张症患者胆囊上皮端粒长度缩短：定量荧光原位杂交测量
DOI：
10.1007/s00535-017-1411-5
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发表时间：
2017
影响因子：
6.3
通讯作者：
Ishiwata Toshiyuki
中科院分区：
文献类型：
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作者：
Aoki Yuto;Aida Junko;Kawano Youichi;Nakamura Ken-ichi;Izumiyama-Shimomura Naotaka;Ishikawa Naoshi;Arai Tomio;Nakamura Yoshiharu;Taniai Nobuhiko;Uchida Eiji;Takubo Kaiyo;Ishiwata Toshiyuki
背景先天性胆道扩张（CBD）是一种先天性畸形，涉及肝外胆管扩张和胰胆管畸形。胰液的持续反流损伤胆道粘膜，导致慢性炎症和胆道（包括胆囊）较高的癌变率。端粒是位于染色体末端的重复DNA序列。端粒功能障碍引起的染色体不稳定在许多器官的癌变中起着重要作用。本研究旨在确定CBD患者胆囊黏膜端粒过度缩短是否发生。方法选取17例CBD患者、10例无胰液反流的胆囊结石患者和17例正常胆囊患者（对照组）（每组患者中位年龄分别为37岁、50岁和53岁）。采用组织切片定量荧光原位杂交法测定胆囊上皮端粒长度，计算标准化端粒与着丝粒比值（NTCR）。结果CBD组、胆囊结石组和对照组的ntcr分别为1.24[四分位间距（IQR） 1.125 ~ 1.52]、1.96 （IQR 1.56 ~ 2.295）和1.77 （IQR 1.48 ~ 2.53）。即使在年轻患者中，CBD组的NTCR也明显小于胆囊结石组和对照组（p分别= 0.003和0.004）。结论胆囊粘膜端粒缩短在CBD患者癌变过程中起重要作用。这些结果支持了对CBD患者预防性手术的指南建议，因为CBD是端粒过度缩短的恶性前病变。
BackgroundCongenital biliary dilatation (CBD) is a congenital malformation involving both dilatation of the extrahepatic bile duct and pancreaticobiliary maljunction. Persistent reflux of pancreatic juice injures the biliary tract mucosa, resulting in chronic inflammation and higher rates of carcinogenesis in the biliary tract, including the gallbladder. Telomeres are repetitive DNA sequences located at the ends of chromosomes. Chromosomal instability due to telomere dysfunction plays an important role in the carcinogenesis of many organs. This study was performed to determine whether excessive shortening of telomeres occurs in the gallbladder mucosa of patients with CBD.MethodsResected gallbladders were obtained from 17 patients with CBD, ten patients with cholecystolithiasis without pancreatic juice reflux, and 17 patients with normal gallbladders (controls) (median age of each group of patients: 37, 50, and 53 years, respectively). The telomere lengths of the gallbladder epithelium were measured by quantitative fluorescence in situ hybridization using tissue sections, and the normalized telomere-to-centromere ratio (NTCR) was calculated.ResultsThe NTCRs in the CBD, cholecystolithiasis, and control groups were 1.24 [interquartile range (IQR) 1.125–1.52], 1.96 (IQR 1.56–2.295), and 1.77 (IQR 1.48–2.53), respectively. The NTCR in the CBD group was significantly smaller than that in the cholecystolithiasis and control groups (p= 0.003 and 0.004, respectively), even in young patients.ConclusionsOur findings indicate that telomere shortening in the gallbladder mucosa plays an important role in the process of carcinogenesis in patients with CBD. These results support the recommendation of established guidelines for prophylactic surgery in patients with CBD because CBD is a premalignant condition with excessive telomere shortening.
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影响因子：
3
作者：
Kamisawa, Terumi;Suyama, Masafumi;Takehara, Hiroo
通讯作者：
Takehara, Hiroo
印度中北部胆结石病和胆囊癌患者的亚端粒甲基化和端粒长度功能障碍
影响因子：
3
作者：
S. Poojary;G. Mishra;Sanjiv Gupta;B. Shrivastav;Pramod K. Tiwari
通讯作者：
Pramod K. Tiwari
影响因子：
3.5
作者：
Lansdorp, PM;Verwoerd, NP;Tanke, HJ
通讯作者：
Tanke, HJ
影响因子：
6.3
作者：
Horaguchi, Jun;Fujita, Naotaka;Harada, Yoshihiro
通讯作者：
Harada, Yoshihiro
2003年日本癌症发病率和发病率：基于日本癌症研究监测（MCIJ）项目中13个基于人群的癌症登记处的数据
DOI：
--
发表时间：
2009
期刊：
Japanese Journal of Clinical Oncology 39(12)
影响因子：
--
作者：
T.Matsuda;T.Marugame;K.Kamo;K.Katanoda;W.Ajiki;T.Sobue
通讯作者：
T.Sobue