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J Thorac Oncol. 2014 Apr;9(4):563-6. doi: 10.1097/JTO.0000000000000093.

A novel fusion of TPR and ALK in lung adenocarcinoma.

Author information

1
Departments 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.

Abstract

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.

PMID:
24736082
DOI:
10.1097/JTO.0000000000000093
[Indexed for MEDLINE]
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