Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins

Proc Natl Acad Sci U S A. 2006 May 9;103(19):7402-7. doi: 10.1073/pnas.0506514103. Epub 2006 May 1.

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.

MeSH terms

  • Amino Acid Sequence
  • Anaplastic Lymphoma Kinase
  • Antibodies / immunology
  • Base Sequence
  • Biopsy
  • Cell Line, Tumor
  • Humans
  • Immunoprecipitation
  • Mass Spectrometry
  • Molecular Sequence Data
  • Neoplasms, Muscle Tissue / metabolism
  • Nuclear Proteins / genetics
  • Oncogene Proteins, Fusion / chemistry
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / immunology
  • Oncogene Proteins, Fusion / metabolism*
  • Protein-Tyrosine Kinases / chemistry
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism*
  • Proteomics
  • RNA, Messenger / genetics
  • Receptor Protein-Tyrosine Kinases
  • Translocation, Genetic / genetics*
  • Tropomyosin / chemistry

Substances

  • Antibodies
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • TPM3 protein, human
  • Tropomyosin
  • nucleophosmin
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases