RESUMO
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.
Assuntos
Transtornos Mieloproliferativos/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Proteínas Tirosina Quinases/genética , Translocação Genética , Adulto , Algoritmos , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular Tumoral , Biologia Computacional , Proteínas do Citoesqueleto , Ordem dos Genes , Células HEK293 , Humanos , Células K562 , Cariotipagem , Masculino , Dados de Sequência Molecular , Transtornos Mieloproliferativos/complicações , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
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