{Reference Type}: Case Reports
{Title}: A Rare STRN-ALK Fusion in Lung Adenocarcinoma Identified Using Next-Generation Sequencing-Based Circulating Tumor DNA Profiling Exhibits Excellent Response to Crizotinib.
{Author}: Yang Y;Qin SK;Zhu J;Wang R;Li YM;Xie ZY;Wu Q;
{Journal}: Mayo Clin Proc Innov Qual Outcomes
{Volume}: 1
{Issue}: 1
{Year}: Jul 2017
暂无{DOI}: 10.1016/j.mayocpiqo.2017.04.003
{Abstract}: The ALK gene fusion has been identified as a new driver gene in non-small 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)-based circulating tumor DNA (ctDNA) analysis. The NGS of the patient's originally paraffin-embedded surgical tumor samples also indicated the fusion. Reverse transcription-polymerase 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 alterations in plasma was closely associated with response to crizotinib treatment. This is the first clinical evidence involving advanced NSCLC due to a rare STRN-ALK fusion and has been effectively treated with crizotinib.