A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing–Based Circulating Tumor DNA Profiling Exhibits Excellent Response to Crizotinib.pdfVIP

CASE REPORT A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation SequencingeBased Circulating Tumor DNA Profiling Exhibits Excellent Response to Crizotinib Yan Yang, MD, PhD; Shu-Kui Qin, MD, PhD; Jian Zhu, MD; Rui Wang, MD; Yu-Mei Li, MD; Zong-Yu Xie, MD; and Qiong Wu, MD, PhD Abstract The ALK gene fusion has been identified as a new driver gene in nonesmall cell lung cancer (NSCLC). It includes the EML4-ALK rearrangement as a recurring event that renders the tumor sensitive to ALK tyrosine kinase inhibitor crizotinib. In addition, several other fusion partners to ALK kinase domain (eg, TFG, KLC1, and KIF5B) have been identified in NSCLC. However, clinical data relevant to response in lung cancer harboring these rare ALK translocations are not fully available. A nonsmoking Chinese male originally diagnosed with “stage Ib lung adenocarcinoma” showed metastases in regional lymph nodes, pleura, and bone 1 year after surgery. The patient refused invasive tissue biopsy, and chemotherapy was administrated, which failed as a first- and second-line treatment. We then identified a rare fusion gene of ALK and Striatin (STRN) using next-generation sequencing (NGS)ebased circulating tumor DNA (ctDNA) analysis. The NGS of the patient’s originally paraffin-embedded surgical tumor samples also indicated the fusion. Reverse transcriptionepolymerase chain reaction and Sanger sequencing further confirmed the results. The STRN-ALK involves the fusion of exon 3 of STRN retaining a coiled-coil domain to exon 20 of ALK containing a kinase domain. The patient was treated with crizotinib and showed excellent clinical, radiographic, and molecular response. Repetitive dynamic ctDNA analysis revealed that the fraction of molecular alte