CUX1-ALK, a Novel ALK Rearrangement That Responds to Crizotinib in Non-Small Cell Lung Cancer

Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer
Meiling ZhangKaihua Lu

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. ALK receptor tyrosine kinase gene (ALK) rearrangement has been identified in 3% to 5% of patients with NSCLC. The most common ALK rearrangement is echinoderm microtubule associated protein like 4 (EML4)-ALK, with several variants that can be targeted by the tyrosine kinase inhibitor crizotinib. In this study using comprehensive next-generation sequencing targeting 416 pan-cancer genes and introns of 16 genes frequently rearranged in cancer, we identified a novel cut-like homeobox 1 gene (CUX1)-ALK fusion gene in a patient with lung adenocarcinoma. The exact CUX1-ALK fusion transcript was determined by RNA sequencing and confirmed by reverse-transcriptase polymerase chain reaction. The oncogenic ability of CUX1-ALK fusion gene was further validated in cells of the line 293T for the activation of anaplastic lymphoma kinase (ALK) self-phosphorylation and downstream signaling pathways. After detection of the CUX1-ALK fusion gene, RNA sequencing analysis of formalin-fixed paraffin-embedded sections from the primary tumor specimen was applied to reveal a 97-nucleotide fragment from CUX1 intron 8 inserted before the nucleotide 53 position in ALK exon 20. Expression o...Continue Reading

Citations

Apr 15, 2020·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Aneta Brisudova, Jozef Skarda
Jul 3, 2019·Journal of Cellular Physiology·Zhongheng WeiYing Wang
Feb 26, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Leiming WangLi Chen
Feb 26, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Weijun MaoMingfeng Zheng
Mar 8, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Liangwei YangGuofang Zhao
Apr 30, 2021·Evolutionary Bioinformatics Online·Xuan LuoMengNa Wu

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