Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation.
Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation.
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DOI：
10.1016/j.celrep.2015.12.005
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发表时间：
2016-02-02
期刊：
影响因子：
8.8
通讯作者：
Gibbs RA
中科院分区：
文献类型：
--
作者：
Gingras MC;Covington KR;Chang DK;Donehower LA;Gill AJ;Ittmann MM;Creighton CJ;Johns AL;Shinbrot E;Dewal N;Fisher WE;Australian Pancreatic Cancer Genome Initiative;Pilarsky C;Grützmann R;Overman MJ;Jamieson NB;Van Buren G 2nd;Drummond J;Walker K;Hampton OA;Xi L;Muzny DM;Doddapaneni H;Lee SL;Bellair M;Hu J;Han Y;Dinh HH;Dahdouli M;Samra JS;Bailey P;Waddell N;Pearson JV;Harliwong I;Wang H;Aust D;Oien KA;Hruban RH;Hodges SE;McElhany A;Saengboonmee C;Duthie FR;Grimmond SM;Biankin AV;Wheeler DA;Gibbs RA
Vater壶腹是一个复杂的细胞环境，腺癌从中产生并形成一组组织病理学异质性肿瘤。为了评估这些肿瘤的分子特征，对 98 例壶腹腺癌进行了评估，并与 44 例远端胆管癌和 18 例十二指肠腺癌进行了比较。基因组分析显示，一半患者和所有三种腺癌中的 WNT 信号通路均存在突变，无论其起源和组织学形态如何。这些肿瘤的特点是 ELF3 失活突变频率高、微卫星不稳定性高、以及常见的局灶性缺失和扩增，表明分子发病机制的共同属性在这些肿瘤中发挥着作用。 WNT 通路激活突变的高频率，加上临床试验中 β 连环蛋白的小分子抑制剂，表明这些患者未来的治疗决策可能会受到基因组分析的指导。
The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas, were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small molecule inhibitors of beta catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis.