Lung Cancer 2018 10 31;124:86-89. Epub 2018 Jul 31.
Division of Hematology-Oncology, Department of Medicine, University of California Irvine School of Medicine, Orange, CA 92868, USA; Chao Family Comprehensive Cancer Center, University of California Irvine, Orange, CA 92868, USA. Electronic address:
Non-small cell lung cancer (NSCLC) has emerged as a paradigm for clinical application of precision medicine as optimal therapy is commonly chosen based on genomic biomarkers identified in a patient's tumor sample. Recurrent driver alterations are well described, however, a need to continually identify rare variants remains clinically relevant. We identified an incident case of advanced NSCLC with a PDGFR-α N848 K activation loop mutation with no other concurrent oncogenic drivers. Amino acid sequence alignment confirmed homology to the imatinib-sensitive KIT N822 K activation loop mutation observed in GIST. The patient achieved a 2-year response to single agent imatinib that is ongoing. While PDGFR-α N848 K is rare among public sequencing databases our cases strongly suggests functional relevance and highlights the importance of studying rare variants in NSCLC.