title: Lack of somatic mutations in the catalytic domains of CREBBP and EP300 genes implies a role for histone deacetylase inhibition in myeloproliferative neoplasms.
abstract: Somatic mutations of the two genes coding for the histone acetyltransferase genes, CREEBP and EP300 have been identified as a pathogenetic mechanism shared by common forms of B-cell non-Hodgkińs lymphomas. A screening for somatic mutations in CREEBP and EP300 genes in patients with myeloproliferative neoplasms (MPNs) has not previously been performed. DNA was purified from diagnostic samples of 56 MPN patients. We designed a mutation screening assay based on denaturing gradient gel electrophoresis and direct sequencing. Our results suggest that CREBBP and EP300 mutations are not major pathogenetic mechanisms of MPNs. The rationale for using HDACi in these patients seems reasonable.
authors.affiliation: Department of Haematology, Copenhagen University Hospital, Copenhagen, Denmark. christenla@gmail.com
authors.forename: Christen Lykkegaard
authors.initials: CL
authors.lastname: Andersen
authors.forename: Hans
authors.initials: H
authors.lastname: Hasselbalch
authors.forename: Kirsten
authors.initials: K
authors.lastname: Grønbæk
mesh_terms: D001483:Base Sequence; D050882:CREB-Binding Protein / Q000235:genetics*; D020134:Catalytic Domain; D004252:DNA Mutational Analysis; D050881:E1A-Associated p300 Protein / Q000235:genetics*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D056572:Histone Deacetylase Inhibitors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; D006655:Histone Deacetylases