OncoTargets and Therapy (Sep 2021)
Identification of a Novel SLC8A1-ALK Fusion and Non-Canonical Expression Significantly Responding to ALK-TKIs in Lung Adenocarcinoma: A Case Report
Abstract
Xingyu Zhu,1,* Yuqi He,2,* Yin Wang,3,* Yan Lei,3 Xiaoxing Su,3 Yifan Liu,1 Shuangxiu Wu,3 Zhengfu He1 1Department of Thoracic Surgery, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 2Monash School of Medicine, Monash University, Clayton, VIC, 3800, Australia; 3Berry Oncology Corporation, Beijing, 102206, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuangxiu WuBerry Oncology Corporation, Beijing, 102206, People’s Republic of ChinaEmail [email protected] HeDepartment of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 East Qing Chun Road, Hangzhou, 310006, Zhejiang, People’s Republic of ChinaTel/Fax +86 571-86006156Email [email protected]: Approximately 2– 7% of patients with non-small cell lung cancer harbor anaplastic lymphoma kinase (ALK) rearrangement events. Of note, typical ALK actionable rearrangements are sensitive to treatment with tyrosine kinase inhibitors (TKIs). However, different types of ALK fusion influence the clinical outcomes of this therapeutic approach. Approximately 10– 40% of patients with ALK-fusion positive non-small cell lung cancer do not response to ALK-TKI therapy. Therefore, it is important to accurately identify the types of ALK rearrangement for appropriate selection of clinical treatment.Case Report: Using a DNA-targeted next-generation sequencing technique, we found a novel solute carrier family 8 member A1 (SLC8A1)-ALK fusion type in a patient with lung adenocarcinoma. Further reverse transcriptase-polymerase chain reaction and Sanger sequencing demonstrated the rearrangement as a B-cell CLL/lymphoma 11A (BCL11A)-ALK fusion at the transcriptional level. The patient showed a rapid and strong response to treatment with crizotinib, which lasted for 9 months. The patient also responded well to treatment with alectinib after developed resistance to crizotinib.Conclusion: A strategy combining DNA-targeted next-generation sequencing with RNA reverse transcriptase-polymerase chain reaction and sequencing, besides fluorescence in situ hybridization and immunohistochemistry, may provide an effective and practical solution for correct identification of partner genes and fusion structures in the diagnosis of ALK rearrangements, particularly for non-canonical expression patterns of ALK fusion events. The combined approach may lead to more benefits for patients.Keywords: lung adenocarcinoma, anaplastic lymphoma kinase rearrangement, tyrosine kinase inhibitor, treatment, case
