Alexander Stoeck, Serguei Lejnine, Andrew Truong, Li Pan, Hongfang Wang, Chongzhi Zang, Jing Yuan, Chris Ware, John MacLean, Philip W Garrett-Engele, Michael Kluk, Jason Laskey, Brian B Haines, Christopher Moskaluk, Leigh Zawel, Stephen Fawell, Gary Gilliland, Theresa Zhang, Brandon E Kremer, Birgit Knoechel, Bradley E Bernstein, Warren S Pear, X Shirley Liu, Jon C Aster, Sriram Sathyanarayanan
UNLABELLED: Next-generation sequencing was used to identify Notch mutations in a large collection of diverse solid tumors. NOTCH1 and NOTCH2 rearrangements leading to constitutive receptor activation were confined to triple-negative breast cancers (TNBC; 6 of 66 tumors). TNBC cell lines with NOTCH1 rearrangements associated with high levels of activated NOTCH1 (N1-ICD) were sensitive to the gamma-secretase inhibitor (GSI) MRK-003, both alone and in combination with paclitaxel, in vitro and in vivo, whereas cell lines with NOTCH2 rearrangements were resistant to GSI...
October 2014: Cancer Discovery