CMTR1-ALK: an ALK fusion in a patient with no response to ALK inhibitor crizotinib

ABSTRACT

The targeted treatment of advanced non-small cell lung cancer (NSCLC) harboring genomic rearrangement of ALK is a paradigm for personalized oncology. More than 15 different ALK fusion partners have been discovered in NSCLC patients. Most of these ALK fusions responded well to the ALK inhibitor crizotinib. Crizotinib is an oral MET/ALK inhibitor used as first-line therapy in the treatment of advanced NSCLC harboring ALK rearrangement. An understanding of the mechanisms by which tumors harbor primary drug resistance or acquired resistance to targeted therapies is critical for predicting which patients will respond to a specific therapy and for the identification of additional targetable pathways to maximize clinical benefits. Cap methyltransferase 1(CMTR1) also known as hMTr1, which is translate a human cap1 2ʹ-o-ribose methyltransferase. Here, we report the newly found ALK fusion, CMTR1-ALK, in a patient who has no response to the ALK inhibitor crizotinib. The results remind us that detecting ALK status is important, but that determining the ALK fusion type and function may be more important for patient.

Keywords:

• Anaplastic lymphoma kinase (ALK)
• CMTR1
• ALK-tyrosine kinase inhibitor (TKI)
• ALK-rearranged NSCLC
• fusion partner gene
• crizotinib

Conflicts of interest

The authors have no conflicts of interest to declare.

Additional information

Funding

This research was supported by National Natural Science Foundation of China. The grant number is [81372834];