A Single-tube Assay for Detecting ALK, ROS1 and RET Fusions in Lung Cancer
Conference Recording Nov 14, 2013
About the SpeakerMaruja Lira is a senior scientist within Precision Medicine group at Pfizer oncology research unit. Her current focus is on identification of patient selection biomarkers through genomic molecular profiling efforts. She has extensive technical experience in analysis of gene expression, copy number, mutation detection, and next generation sequencing. She is a key developer of a transcript-based assay for screening ALK, ROS1, and RET fusions in lung cancer.
Abstract7-8% of non-small cell lung carcinomas (NSCLC) harbor oncogenic fusions involving ALK, ROS1 and RET. While tumors harboring ALK fusions are highly sensitive to crizotinib, emerging preclinical and clinical data have demonstrated that patients with ROS1 or RET fusions may also benefit from the inhibitors targeting the two kinases. Currently, no robust single assay has been developed for the simultaneous detection of three targetable fusions in lung cancer. Utilizing a transcript-based method, we designed a combination of 3’ over-expression and fusion-specific detection strategies to detect for presence/absence of ALK, ROS1 and RET fusion transcripts in NSCLC tumors. We successfully validated the assay in 263 NSCLC specimens and show that the assay is highly sensitive and specific. For ALK, our results were highly concordant (100% and 97.8% respectively) to prior results obtained by FISH (n=52) and IHC (n=179). We identified six ROS1 and twelve RET fusion-positive tumors and confirmed fusion status by RT-PCR followed by sequencing. As a single-tube assay, our test shows promise as a more practical and cost-effective screening modality for the detection of rare but targetable fusions in lung cancer.