AUTHOR=Du Jia , Wang Baoming , Li Mengxia , Wang Chunyang , Ma Tonghui , Shan Jinlu 

TITLE=A Novel Intergenic Gene Between SLC8A1 and PKDCC-ALK Fusion Responds to ALK TKI WX-0593 in Lung Adenocarcinoma: A Case Report

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.898954

DOI=10.3389/fonc.2022.898954

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Expanding the druggable novel anaplastic lymphoma kinase (<italic>ALK</italic>) fusions list is crucial to the precise treatment of patients with cancer with positive <italic>ALK</italic> fusions. The <italic>intergenic-ALK</italic> fusions accounted for a substantial proportion of <italic>ALK</italic> fusions. However, they were typically considered of limited clinical significance due to the obscure functional partners. In this case report, a patient carrying <italic>intergenic-ALK</italic> fusion presents an excellent outcome after taking the new second-generation tyrosine kinase inhibitor (TKI) candidate, WX-0593.</p></sec><sec><title>Case Presentation</title><p>A 47-year-old Chinese female patient diagnosed with IVB lung adenocarcinoma was admitted to the hospital with large dimension lesions in the left lobe of the lung. After 1 week of first line chemotherapy, no response was found. A novel <italic>ALK</italic> rearrangement generated by a fusion of the intergenic region between <italic>SLC8A1</italic> and <italic>PKDCC</italic> to the intron 19 of <italic>ALK</italic> was presented after next-generation sequencing and was further confirmed by Sanger’s sequencing. High expression of <italic>ALK</italic> was revealed by immunohistochemistry. The patient was directed to engage in phase III clinical trial (NCT04632758) and received an orally active second-generation <italic>ALK</italic> inhibitor WX-0593. Over the course of 17 months, the partial response was obtained without significant side effects.</p></sec><sec><title>Conclusion</title><p>In summary, a patient with non–small cell lung cancer harboring a novel <italic>intergenic-ALK</italic> fusion, whose intergenic breakpoint was located between <italic>SLC8A1</italic> and <italic>PKDCC</italic>, benefited from a potent <italic>ALK</italic> TKI candidate WX-0593. This finding extended the scope of targetable <italic>ALK</italic> fusions. More importantly, it highlighted the advantages of next-generation sequencing in identifying rare but functional <italic>ALK</italic> fusions, which eventually benefit patients.</p></sec>