Lung adenocarcinoma patients with novel ALK fusion variants and their clinical responses to ALK inhibitors

Abstract

Dear Editor, Lung cancer is one of the most common cancers worldwide and is associated with high mortality. Anaplastic lymphoma kinase (ALK) rearrangement, an oncogenic driver, has been identified in 5% to 6% of patients with non-small cell lung cancer (NSCLC) [1]. The first identified and the most common ALK fusion partner is echinoderm microtubule-associated protein-like 4 (EML4) [2]. With the broad application of next-generation sequencing (NGS), an increasing number of novel ALK fusions have been reported. Many ALK tyrosine kinase inhibitors (ALK-TKIs), including crizotinib, brigatinib, ceritinib, and ensartinib, have been approved to treat ALK-positive NSCLC patients, and their efficacy may be affected by different ALK fusion variants [3]. Here, we report two novel ALK fusions, MAPRE3-ALK and PKNOX2-ALK, detected by an NGS panel targeting 425 cancer-related genes (Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China) [4] in two metastatic lung adenocarcinoma patients who then received ALK-TKI treatments. The drug efficacy of the two novel fusions reported here could have significant referential value and provide useful therapeutic strategies for treating ALK-positive patients. Case number 1 was a 38-year-old female who was referred to the Second Hospital of Dalian Medical University (Dalian, China) in December 2018 after a routine physical examination. Her chest computed tomography