%0 Journal Article
%T Mutational profiling reveals PIK3CA mutations in gallbladder carcinoma
%A Vikram Deshpande
%A Afamefuna Nduaguba
%A Stephanie M Zimmerman
%A Sarah M Kehoe
%A Laura E MacConaill
%A Gregory Y Lauwers
%A Cristina Ferrone
%A Nabeel Bardeesy
%A Andrew X Zhu
%A Aram F Hezel
%J BMC Cancer
%D 2011
%I BioMed Central
%R 10.1186/1471-2407-11-60
%X To better characterize mutations in established known oncogenes and tumor suppressor genes we tested a mass spectrometric based platform to interrogate common cancer associated mutations across a panel of 77 formalin fixed paraffin embedded archived BTC cases.Mutations among three genes, KRAS, NRAS and PIK3CA were confirmed in this cohort. Activating mutations in PIK3CA were identified exclusively in GBC (4/32, 12.5%). KRAS mutations were identified in 3 (13%) intra-hepatic cholangiocarcinomas and 1 (33%) perihillar cholangiocarcinoma but were not identified in gallbladder carcinomas and extra-hepatic cholangiocarcinoma.The presence of activating mutations in PIK3CA specifically in GBC has clinical implications in both the diagnosis of this cancer type, as well as the potential utility of targeted therapies such as PI3 kinase inhibitors.Biliary tract cancer (BTC) includes a spectrum of invasive adenocarcinomas including cholangiocarcinomas arising from within the liver parenchyma, peri-hilar, or distal biliary tree, as well as carcinoma arising from the gallbladder (GBC). Regardless of the site of origin, these tumors display a remarkably similar histologic appearance, variable amount of gland formation, and an exuberant desmoplastic stromal reaction. These tumors share an anatomic origin in the biliary system; however, there are important differences in disease behavior, molecular profiles, and sensitivity to therapy. In general GBC tends to exhibit greater initial sensitivity to chemotherapy but confers a shorter overall survival compared with cholangiocarcinoma (CC)[1]. Historically, treatment for BTC has not taken into account the anatomic site of origin of the tumor or molecular profile and the mainstay of treatment is cytotoxic chemotherapy, as these tumors are commonly diagnosed at advanced stages when surgical resection is not an option.While a spectrum of mutations in established oncogenes and tumor suppressors have been identified in BTC the real frequency
%U http://www.biomedcentral.com/1471-2407/11/60