High‐throughput sequencing detection and ensartinib treatment of lung cancer harboring NTRK1 fusion

• Published in: Cancer communications (London, England) Vol. 41; no. 2; pp. 192 - 196
• Main Authors: Song, Zhengbo, Xu, Chunwei, Pu, Xingxiang, Zhu, Youcai, Wang, Wenxian, Li, Xingliang, Gao, Yanqiu, Zhu, Wenliang, He, Yunwei, Wu, Lin, Mao, Li, Chen, Li, Chen, Ming
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-02-2021; John Wiley and Sons Inc; Wiley
• Subjects: Antigens; Cancer therapies; Epidermal growth factor; Genes; Kinases; Letter to the Editor; Letters to the Editor; Lung cancer; Lymphoma; Medical imaging; Mutation; Patients; Proteins; Software; Spermatogenesis; United States > US
• ISSN: 2523-3548; 2523-3548
• DOI: 10.1002/cac2.12133

Abbreviations NGS next-generation sequencing SNV single nucleotide variation indel insertion-or-deletion PANO-Seq parallel amplification and numerically optimized sequencing NTRK neurotrophic receptor tyrosine kinase LoD limit of detection MAF mutant allele frequency TKI tyrosine receptor kinase inhibitor EGFR epidermal growth factor receptor KRAS KRAS proto-oncogene PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha BRAF B-Raf proto-oncogene, serine/threonine kinase MET MET proto-oncogene ALK anaplastic lymphoma kinase ROS1 ROS proto-oncogene 1 RET ret proto-oncogene NRG1 neuregulin 1 CHMP2A charged multivesicular body protein 2A HLA-DRB1 human leukocyte antigen DRB1 TPR translocated promoter region protein SQSTM1 sequestosome 1 RFWD2 RING finger and WD repeat domain 2 MSN moesin PR partial response SD stable disease PD progressive disease SPATA46 spermatogenesis associated 46 LMNA lamin A/C ETV6 ETS translocation variant 6 Dear Editor, Although fusion events involving neurotrophic receptor tyrosine kinase 1, 2, and 3 genes (NTRK1, NTRK2, and NTRK3, encoding TRKA/B/C respectively) were found in diverse tumor types, only 0.1%-0.3% of lung cancer patients harbor an NTRK (and mostly NTRK1) fusion as the primary oncogenic event [ 1]. Durable responses to tyrosine receptor kinase inhibitors (TKI) such as larotrectinib and entrectinib have been observed in a broad range of malignancies [ 5, 6], and the next-generation inhibitor repotrectinib exhibited promising activity against solvent-front substitution mutations [ 7], while inhibitors such as crizotinib initially developed for other kinases may also be effective in targeting TRK [ 8]. TRK-fusion protein consists of an intact oncogenic kinase domain, either constitutively activated by a 5’ partner domain or overexpressed due to a stronger partner gene promoter. Since the RNA-containing tissue specimen was no longer obtainable, a modified assay targeting NTRK1 introns 7-14 (Fig. 1A) was performed, revealing a TPR-NTRK1 fusion in the plasma cell-free DNA, validated by Sanger sequencing (Fig. 1E).