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Updated: May 1, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
A novel fusion of TPR and ALK in lung adenocarcinoma
Yoon-La Choi1, Maruja E Lira, Mineui Hong
1Departments of *Pathology and **Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea; †Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; ‡Oncology Research Unit, Pfizer Inc., San Diego, California; §Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea; ‖ArcherDx Inc., Boulder, Colorado; ¶Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; and #Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Introduction:
Anaplastic lymphoma kinase (ALK) fusion is the most common mechanism for overexpression and activation in non-small-cell lung carcinoma. Several fusion partners of ALK have been reported, including echinoderm microtubule-associated protein-like 4, TRK-fused gene, kinesin family member 5B, kinesin light chain 1 (KLC1), protein tyrosine phosphatase and nonreceptor type 3, and huntingtin interacting protein 1 (HIP1).
Methods And Results:
A 60-year-old Korean man had a lung mass which was a poorly differentiated adenocarcinoma with ALK overexpression. By using an Anchored Multiplex polymerase chain reaction assay and sequencing, we found that tumor had a novel translocated promoter region (TPR)-ALK fusion. The fusion transcript was generated from an intact, in-frame fusion of TPR exon 15 and ALK exon 20 (t(1;2)(q31.1;p23)). The TPR-ALK fusion encodes a predicted protein of 1192 amino acids with a coiled-coil domain encoded by the 5'-2 of the TPR and juxtamembrane and kinase domains encoded by the 3'-end of the ALK.
Conclusions:
The novel fusion gene and its protein TRP-ALK, harboring coiled-coil and kinase domains, could possess transforming potential and responses to treatment with ALK inhibitors. This case is the first report of TPR-ALK fusion transcript in clinical tumor samples and could provide a novel diagnostic and therapeutic candidate target for patients with cancer, including non-small-cell lung carcinoma.
Insights
A novel translocated promoter region (TPR)-anaplastic lymphoma kinase (ALK) fusion was identified in a non-small-cell lung carcinoma patient. This TPR-ALK fusion may serve as a new diagnostic and therapeutic target for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anaplastic lymphoma kinase (ALK) fusions are common drivers in non-small-cell lung carcinoma.
- Known ALK fusion partners include EM L4, NCL, KIF5B, KLC1, PTPRN3, and HIP1.
Observation:
- A 60-year-old Korean male presented with a lung mass diagnosed as poorly differentiated adenocarcinoma with ALK overexpression.
- Anchored Multiplex PCR and sequencing revealed a novel translocated promoter region (TPR)-ALK fusion in the tumor.
- The fusion involved TPR exon 15 and ALK exon 20, resulting in a t(1;2)(q31.1;p23) translocation.
Findings:
- The novel TPR-ALK fusion transcript encodes a predicted protein of 1192 amino acids.
- This protein contains a coiled-coil domain from TPR and juxtamembrane/kinase domains from ALK.
- This represents the first reported case of a TPR-ALK fusion in clinical tumor samples.
Implications:
- The TPR-ALK fusion protein may possess oncogenic potential due to its functional domains.
- This novel fusion could be a target for ALK inhibitors in NSCLC treatment.
- TPR-ALK fusion represents a new diagnostic and therapeutic candidate for cancer patients, particularly those with NSCLC.
