Case Report: Structurally Rare EML4-ALK Identified by Next Generation Sequencing in a Patient with NSCLC with Bilateral Ovarian Metastases

The <i>EML4-ALK</i> oncogene is a fusion of the <i>EML4</i> and <i>ALK</i> genes and is found in approximately 5-6% of the cases of non-small cell lung cancer (NSCLC). Herein, we present a unique case of lung adenocarcinoma with metastases to the bilateral ovaries harboring a rare <i>EML4-ALK</i> fusion gene variant in a 52-year-old patient. The patient had initially received a diagnosis of ovarian cancer, then had undergone neo-adjuvant chemotherapy followed by a surgical resection. Despite two cycles of adjuvant chemotherapy consisting of carboplatin and gemcitabine, CT revealed that the pleural effusion had increased from it before chemotherapy, and the shortness of breath worsened. Molecular profiling revealed an <i>EML4-ALK</i> rearrangement containing <i>ALK -EML4</i> and <i>ALK -NPR2</i> fusion genes. The diagnosis was changed to primary lung adenocarcinoma with metastases to the bilateral ovaries based on a pathological reevaluation. Treatment with alectinib, a second-generation ALK-tyrosine kinase inhibitor, led to a partial response of 18 months' duration, and the shortness of breath improved. No adverse events related to the alectinib therapy occurred. To assess the unique structure of the fusion genes, RNA sequencing was performed. An intronic sequence from both <i>ALK</i> and <i>EML4</i> was found between <i>ALK</i> and <i>EML4</i> exon, possibly because of an unusual insertion of a gene fragment derived from <i>NRP2</i>, indicated by the panel sequencing results. Variations in the drug response among <i>EML4-ALK</i> fusion variants highlight the importance of understanding their molecular structure. Further investigation is warranted to refine fusion gene detection methods and assess the therapeutic implications of rare fusion variants.