title: Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated myeloproliferative neoplasm.
abstract: Gene fusions involving the catalytic domain of tyrosine kinases (TKs) are found in a variety of hematological and solid tumor malignancies. Clinically, TK fusions have emerged as prime targets for therapy with small molecule kinase inhibitors. Unfortunately, identification of TK fusions has been hampered by experimental limitations. Here, we developed version 2.0 of a genomically based systematic kinase fusion screen and used it to detect a novel imatinib-sensitive C6orf204-PDGFRB fusion in a patient with precursor T lymphoblastic lymphoma (T-ALL) and an associated myeloproliferative neoplasm with eosinophilia. These data validate the ability of this targeted capture-sequencing approach to detect TK fusion events in small amounts of DNA extracted directly from patient samples.
authors.affiliation: Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.
authors.forename: Juliann
authors.initials: J
authors.lastname: Chmielecki
authors.forename: Martin
authors.initials: M
authors.lastname: Peifer
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.forename: Katherine
authors.initials: K
authors.lastname: Hutchinson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Giltnane
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: Socci
authors.forename: Clayton J
authors.initials: CJ
authors.lastname: Hollis
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Dean
authors.forename: Ashwini
authors.initials: A
authors.lastname: Yenamandra
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
authors.forename: Annette S
authors.initials: AS
authors.lastname: Kim
authors.forename: Utpal P
authors.initials: UP
authors.lastname: Davé
authors.forename: Roman K
authors.initials: RK
authors.lastname: Thomas
authors.forename: William
authors.initials: W
authors.lastname: Pao
mesh_terms: D000328:Adult; D000465:Algorithms; D000595:Amino Acid Sequence; D001483:Base Sequence; D045744:Cell Line, Tumor; D019295:Computational Biology; D003598:Cytoskeletal Proteins; D023061:Gene Order; D057809:HEK293 Cells; D006801:Humans; D020014:K562 Cells; D007621:Karyotyping; D008297:Male; D008969:Molecular Sequence Data; D009196:Myeloproliferative Disorders / Q000150:complications / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014178:Translocation, Genetic
chemical_list: C573619:CEP85L protein, human; D003598:Cytoskeletal Proteins; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases