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Updated: Aug 9, 2026
Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase
Kojo S J Elenitoba-Johnson1, David K Crockett, Jonathan A Schumacher
1Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. kojo.elenitobaj@path.utah.edu
Abstract:
The anaplastic lymphoma kinase (ALK) on 2p23 is a tyrosine kinase that forms chimeric fusions with numerous translocation partners. We describe a mass spectrometry-based approach for the identification of ALK fusion partners. This approach accurately identified the nucleophosmin (NPM)-ALK fusion protein in an anaplastic large cell lymphoma (ALCL)-derived cell line carrying the t(2;5)(p23;q35), and the TPM3-ALK in a clinical biopsy of inflammatory myofibroblastic tumor (IMT) carrying the t(1;2)(q21;p23). This study shows the ability of mass spectrometry to identify oncogenic chimeric proteins resulting from chromosomal rearrangements. This strategy can be adapted for the identification of known and unknown translocation partners of chimeric ALK fusion proteins involved in oncogenesis.
Insights
Mass spectrometry can identify anaplastic lymphoma kinase (ALK) fusion proteins, which drive cancer. This method successfully detected NPM-ALK in lymphoma and TPM3-ALK in tumor samples, aiding oncogenic protein discovery.
Area of Science:
- Oncology
- Proteomics
- Genetics
Background:
- Anaplastic lymphoma kinase (ALK) is a tyrosine kinase implicated in various cancers due to its fusion with translocation partners.
- Identifying these ALK fusion proteins is crucial for understanding oncogenesis and developing targeted therapies.
Purpose of the Study:
- To present a mass spectrometry-based strategy for identifying anaplastic lymphoma kinase (ALK) fusion partners.
- To demonstrate the efficacy of this approach in detecting known ALK fusion proteins in relevant cancer models.
Main Methods:
- Utilized mass spectrometry for the identification of chimeric anaplastic lymphoma kinase (ALK) fusion proteins.
- Applied the method to an anaplastic large cell lymphoma (ALCL) cell line and a clinical inflammatory myofibroblastic tumor (IMT) biopsy.
Main Results:
- Accurately identified the nucleophosmin (NPM)-ALK fusion protein in an ALCL cell line with a t(2;5) translocation.
- Successfully detected the TPM3-ALK fusion protein in an IMT biopsy with a t(1;2) translocation.
Conclusions:
- Mass spectrometry is a powerful tool for identifying oncogenic chimeric proteins resulting from chromosomal rearrangements.
- This strategy is adaptable for discovering novel and known anaplastic lymphoma kinase (ALK) translocation partners involved in cancer development.
