Nastase Anca, Teo Jin Yao, Heng Hong Lee, Ng Cedric Chuan Young, Myint Swe Swe, Rajasegaran Vikneswari, Loh Jia Liang, Lee Ser Yee, Ooi London Lucien, Chung Alexander Yaw Fui, Chow Pierce Kah Hoe, Cheow Peng Chung, Wan Wei Keat, Azhar Rafy, Khoo Avery, Xiu Sam Xin, Alkaff Syed Muhammad Fahmy, Cutcutache Ioana, Lim Jing Quan, Ong Choon Kiat, Herlea Vlad, Dima Simona, Duda Dan G, Teh Bin Tean, Popescu Irinel, Lim Tony Kiat Hon
Laboratory of Cancer Epigenome, National Cancer Centre SingaporeSingapore; Centre of Digestive Diseases and Liver Transplantation, Fundeni Clinical InstituteBucharest, Romania.
Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital Singapore.
Am J Cancer Res. 2017 Mar 1;7(3):484-502. eCollection 2017.
is one of the most commonly mutated genes in a broad variety of tumors. The mechanisms that involve in ampullary cancer progression remains elusive. Here, we evaluated the frequency of and mutations in ampullary adenomas and adenocarcinomas and in duodenal adenocarcinomas from two cohorts of patients from Singapore and Romania, correlated with clinical and pathological tumor features, and assessed the functional role of . In the ampullary adenocarcinomas, the frequency of and mutations was 34.7% and 8.2% respectively, with a loss or reduction of ARID1A protein in 17.2% of the cases. mutational status was significantly correlated with ARID1A protein expression level (P=0.023). There was a significant difference in frequency of mutation between Romania and Singapore (2.7% versus 25%, P=0.04), suggestive of different etiologies. One somatic mutation was detected in the ampullary adenoma group. studies indicated the tumor suppressive role of . Our results warrant further investigation of this chromatin remodeller as a potential early biomarker of the disease, as well as identification of therapeutic targets in mutated ampullary cancers.
是多种肿瘤中最常发生突变的基因之一。壶腹癌进展所涉及的机制仍不清楚。在此，我们评估了来自新加坡和罗马尼亚的两组患者的壶腹腺瘤、腺癌以及十二指肠腺癌中 和 突变的频率，将其与临床和病理肿瘤特征相关联，并评估了 的功能作用。在壶腹腺癌中， 和 突变的频率分别为34.7%和8.2%，17.2%的病例中ARID1A蛋白缺失或减少。 突变状态与ARID1A蛋白表达水平显著相关（P = 0.023）。罗马尼亚和新加坡之间 突变频率存在显著差异（2.7%对25%，P = 0.04），提示病因不同。在壶腹腺瘤组中检测到1个体细胞突变。 研究表明了 的肿瘤抑制作用。我们的结果值得进一步研究这种染色质重塑因子作为该疾病潜在的早期生物标志物，以及确定 突变的壶腹癌中的治疗靶点。
