A novel fusion of TPR and ALK in lung adenocarcinoma

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

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Exons / genetics
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Nuclear Pore Complex Proteins / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Polymerase Chain Reaction
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Translocation, Genetic / genetics*

Substances

  • Nuclear Pore Complex Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • TPR protein, human
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases