Abstract 2339: Prevalence of MET expression, activating mutations of KRAS and IDH1/2, and ROS1 fusions in cholangiocarcinoma patient tumor samples.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Cholangiocarcinoma (CCA) originates from biliary tract epithelium and can be classified anatomically into intrahepatic or extrahepatic CCA. Although a relatively rare disease in the United States and Europe, the incidence of intrahepatic CCA is on the rise with unknown causes. CCA incidence is higher in Asia and the etiology is associated with infections such as liver fluke and hepatitis B/C. Prognosis at diagnosis is poor with median survival time of C and c.183A>T for Q61H), 5 IDH1 mutations (R132G, R132S, R132H, R132C, R132L), and 5 IDH2 mutations (R172G, R172M, R172K, R172W, R172S) were analyzed. Overall, 25% of analyzed samples were positive for KRAS mutation, and G12D was the predominant mutation (∼60%). One-third of Asian samples were positive for KRAS mutation, whereas less than one-fifth of non-Asian samples contained KRAS mutations. For IDH1, the frequency of mutation was less than 10% overall, and the majority of patients with IDH1 mutations were non-Asian. The R132C mutation was the predominant IDH1 mutation, and all tissues that were positive for IDH1 mutations were of intrahepatic origin. Interestingly, 2 out of the 7 samples positive for IDH1 mutations (R132C) were also positive for G12D KRAS mutation. There is no trend of MET expression correlating with either KRAS or IDH1 mutations. IDH2 analyses by castPCR and FISH studies examining ROS1 gene fusion are ongoing. Based on these data, inhibitors of receptor tyrosine kinases and their signaling pathways such as MET and ROS1 may merit clinical evaluation in CCA patients. LY2801653, a MET inhibitor which also has inhibitory activity against ROS1 and MKNK1/2 is currently in phase 1 clinical testing in patients with advanced cancer (trial I3O-MC-JSBA, [NCT01285037][1]). Citation Format: Megan N. Thobe, S. Betty Yan, Kelly M. Credille, Aejaz Nasir, Jessica A. Roseberry Baker, Mary Lajiness, Nathan A. Brooks, Darryl W. Ballard, Donna M. Farley, Victoria L. Peek, Suzane L. Um, G. Jason Jin, Raymond Gilmour, Christoph Reinhard, Jeremy R. Graff, Andrew E. Schade, Aaron M. Gruver, Bruce Colligan, Larry Douglass, Julia Carter, Richard A. Walgren. Prevalence of MET expression, activating mutations of KRAS and IDH1/2, and ROS1 fusions in cholangiocarcinoma patient tumor samples. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2339. doi:10.1158/1538-7445.AM2013-2339 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01285037&atom=%2Fcanres%2F73%2F8_Supplement%2F2339.atom