Systematic screen for tyrosine kinase rearrangements identifies a novel C6orf204-PDGFRB fusion in a patient with recurrent T-ALL and an associated myeloproliferative neoplasm

Genes Chromosomes Cancer. 2012 Jan;51(1):54-65. doi: 10.1002/gcc.20930. Epub 2011 Sep 21.

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.

MeSH terms

  • Adult
  • Algorithms
  • Amino Acid Sequence
  • Base Sequence
  • Cell Line, Tumor
  • Computational Biology
  • Cytoskeletal Proteins
  • Gene Order
  • HEK293 Cells
  • Humans
  • K562 Cells
  • Karyotyping
  • Male
  • Molecular Sequence Data
  • Myeloproliferative Disorders / complications
  • Myeloproliferative Disorders / genetics*
  • Oncogene Proteins, Fusion / genetics*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Protein-Tyrosine Kinases / genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Translocation, Genetic*

Substances

  • CEP85L protein, human
  • Cytoskeletal Proteins
  • Oncogene Proteins, Fusion
  • Protein-Tyrosine Kinases