Research Project
8833122
DESCRIPTION (provided by applicant): In the US, lung cancer will add 224,210 new cases and cause 159,260 deaths in 2014. Non- small cell lung cancer (NSCLC) accounts for 80% of lung cancer. The availability of targeted therapies directed to driver oncogenes such as EGFR mutations and gene fusions (e.g., EML4- ALK) in recent years has transformed the management of NSCLC. These advances have also created an unprecedented challenge to conduct multiple molecular testing using limited diagnostic materials. In many settings, 40-50% of NSCLC patients present with advanced disease and are simultaneously diagnosed, staged and their tumors molecularly tested for targeted therapy using fine needle aspiration (FNA)-derived cytology specimen obtained during endobronchial ultrasound (EBUS). Liquid-based cytology slides, especially ThinPrep slides, have proven superior to formalin-fixed paraffin-embedded (FFPE) cell blocks for assessing ALK gene status by DNA fluorescent in situ hybridization (FISH). However, the number of ThinPrep slides that can be prepared from a typical EBUS-FNA specimen is limited (usually 2-3). In order to perform multiple testing, an in situ method with multiplexing capability beyond conventional FISH and immunohistochemistry (IHC) is needed. In this Phase I study, we propose to leverage the high sensitivity and multiplexing capability of a recently developed RNA in situ hybridization technology (RNAscope(R)) to develop a novel companion diagnostic algorithm that can efficiently and accurately detect multiple rare but actionable oncogenic gene fusions (ALK, ROS1, RET, NTRK1 and others) in NSCLC patients using FNA-derived ThinPrep slides.
