Molecular profiling of cholangiocarcinoma shows potential for targeted therapy treatment decisions
Molecular profiling of cholangiocarcinoma shows potential for targeted therapy treatment decisions
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DOI：
10.1016/j.humpath.2012.11.006
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发表时间：
2013-07-01
期刊：
影响因子：
3.3
通讯作者：
Kipp, Benjamin R.
中科院分区：
文献类型：
--
作者：
Voss, Jesse S.;Holtegaard, Leonard M.;Kipp, Benjamin R.
胆管癌是一种高度致命的胆道癌。肝内胆管细胞癌的发病率在全球范围内呈上升趋势。尽管在过去的十年里技术进步了，但人们对这些肿瘤中发生的躯体变化知之甚少。本研究的目的是确定切除的胆管细胞癌标本中常见癌基因的频率，为诊断为胆管细胞癌的患者提供潜在的治疗靶点。来自94个切除的胆管癌细胞的福尔马林固定、石蜡包埋的组织块被用来从包含超过20%的肿瘤的区域提取DNA。使用Sequenom Massarray OncoCarta突变概况分析小组(加利福尼亚州圣地亚哥)对标本进行评估。这个基质辅助的激光解吸/电离飞行时间质谱仪单一基因分型小组评估了238个体细胞突变的19个癌基因。在94例胆管细胞癌中，有23例发现了25个基因突变：KRAS(n=12)、PIK3CA(n=5)、MET(n=4)、EGFR(n=1)、BRAF(n=2)和NRAS(n=1)。27例肝外胆管细胞癌中有7例(26%)发生突变，67例肝内胆管细胞癌中有16例(24%)发生突变。当结合IDH1/2检测时，94例胆管细胞癌中有40例(43%)有可检测到的突变。MassARRAY技术可以利用石蜡包埋组织来检测各种癌基因的突变。体细胞突变的临床检测可能会推动未来胆管癌的个性化治疗选择。检测到的各种突变表明，对于胆道恶性肿瘤患者的治疗，多重突变检测方法可能是必要的。(C)2013 Elsevier Inc.保留所有权利。
Cholangiocarcinoma is a highly lethal cancer of the biliary tract. The intrahepatic subtype of cholangiocarcinoma is increasing in incidence globally. Despite technologic advancements over the past decade, little is known about the somatic changes that occur in these tumors. The goal of this study was to determine the frequency of common oncogenes in resected cholangiocarcinoma specimens that could provide potential therapeutic targets for patients diagnosed with cholangiocarcinoma. Formalin-fixed, paraffin-embedded tissue blocks from 94 resected cholangiocarcinomas were used to extract DNA from areas comprising more than 20% tumor. Specimens were evaluated using the Sequenom MassARRAY OncoCarta Mutation Profiler Panel (San Diego, CA). This matrix-assisted laser desorption/ionization-time of flight mass spectrometry single genotyping panel evaluates 19 oncogenes for 238 somatic mutations. Twenty-five mutations were identified in 23 of the 94 cholangiocarcinomas within the following oncogenes: KRAS (n = 12), PIK3CA (n = 5), MET (n = 4), EGFR (n = 1), BRAF (n = 2), and NRAS (n = 1). Mutations were identified in 7 (26%) of 27 extrahepatic cholangiocarcinomas and 16 (24%) of 67 intrahepatic cholangiocarcinomas. When combined with IDH1/2 testing, 40 (43%) of the 94 cholangiocarcinomas had a detectable mutation. MassARRAY technology can be used to detect mutations in a wide variety of oncogenes using paraffin-embedded tissue. Clinical testing for somatic mutations may drive personalized therapy selection for cholangiocarcinomas in the future. The variety of mutations detected suggests that a multiplexed mutation detection approach may be necessary for managing patients with biliary tract malignancy. (C) 2013 Elsevier Inc. All rights reserved.