Clinical and Molecular Traits of a Novel SPECC1L-ALK Fusion in a Patient with Advanced Non-Small Cell Lung Cancer.

Anaplastic lymphoma kinase (ALK) fusions account for 5-7% of non-small cell lung cancer (NSCLC) patients, the therapeutic approaches for which have significantly evolved in the last few years. However, the response to target therapies remains heterogeneous, partially due to the many different ALK fusion variants reported to date. Rare fusion variants have also been discovered, but their role in influencing responses to ALK inhibitors (ALKis) remains poorly elucidated. Laboratory investigation at both the tissue and protein levels, and a molecular profile by next-generation sequencing (NGS) were performed on a lung biopsy sample from one patient with poorly differentiated adenocarcinoma. An in silico prediction model using ColabFold software v1.5.5 was used to model and predict the entire structure of the chimeric aberrant ALK protein. Here, we report a case of a former smoker, a 60-year-old man, diagnosed with NSCLC and undergoing ALK translocation. He received first-, second- and third-generation ALK protein inhibitors (ALKis), showing a clinical benefit for about 4 years. IHC analysis and the molecular examination of the tissue biopsy indicated a positive staining for ALK and a novel