title: Fusion peptides from oncogenic chimeric proteins as putative specific biomarkers of cancer.
abstract: Chromosomal translocations encoding chimeric fusion proteins constitute one of the most common mechanisms underlying oncogenic transformation in human cancer. Fusion peptides resulting from such oncogenic chimeric fusions, though unique to specific cancer subtypes, are unexplored as cancer biomarkers. Here we show, using an approach termed fusion peptide multiple reaction monitoring mass spectrometry, the direct identification of different cancer-specific fusion peptides arising from protein chimeras that are generated from the juxtaposition of heterologous genes fused by recurrent chromosomal translocations. Using fusion peptide multiple reaction monitoring mass spectrometry in a clinically relevant scenario, we demonstrate the specific, sensitive, and unambiguous detection of a specific diagnostic fusion peptide in clinical samples of anaplastic large cell lymphoma, but not in a diverse array of benign lymph nodes or other forms of primary malignant lymphomas and cancer-derived cell lines. Our studies highlight the utility of fusion peptides as cancer biomarkers and carry broad implications for the use of protein biomarkers in cancer detection and monitoring.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109;
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Conlon
authors.forename: Venkatesha
authors.initials: V
authors.lastname: Basrur
authors.forename: Delphine
authors.initials: D
authors.lastname: Rolland
authors.forename: Thomas
authors.initials: T
authors.lastname: Wolfe
authors.forename: Alexey I
authors.initials: AI
authors.lastname: Nesvizhskii
authors.forename: Michael J
authors.initials: MJ
authors.lastname: MacCoss
authors.forename: Megan S
authors.initials: MS
authors.lastname: Lim
authors.forename: Kojo S J
authors.initials: KS
authors.lastname: Elenitoba-Johnson
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D010455:Peptides; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases