Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins.
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.
Elenitoba-Johnson
Kojo S J
KS
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. kojo.elenitobaj@path.utah.edu
Crockett
David K
DK
Schumacher
Jonathan A
JA
Jenson
Stephen D
SD
Coffin
Cheryl M
CM
Rockwood
Alan L
AL
Lim
Megan S
MS
D000595:Amino Acid Sequence; D000077548:Anaplastic Lymphoma Kinase; D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D001706:Biopsy; D045744:Cell Line, Tumor; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009379:Neoplasms, Muscle Tissue / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D014178:Translocation, Genetic / Q000235:genetics*; D014335:Tropomyosin / Q000737:chemistry
D000906:Antibodies; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C498783:TPM3 protein, human; D014335:Tropomyosin; D000090243:Nucleophosmin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases