Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia

作者: Hiroto Inaba , Christine Hartford , Ching-hon Pui , Alberto Pappo , Michael Edmonson

DOI: 10.1371/JOURNAL.PGEN.1005262

关键词: Cancer researchBiologyLeukemiaWild typeGermline mutationSomatic cellGermlineMyeloid leukemiaProbandETV6Genetics(clinical)GeneticsEcology, Evolution, Behavior and SystematicsMolecular biology

摘要: Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline p. L349P mutation kindred affected by thrombocytopenia and ALL. A second N385fs was identified an unrelated characterized thrombocytopenia, secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from proband showed deletion of wild type with retention N385fs. Enforced expression mutants revealed normal transcript protein levels, but impaired nuclear localization. Accordingly, these exhibited significantly reduced ability regulate transcription target genes. Our findings highlight role for predisposition.

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