title: Reduced DNA methylation and hydroxymethylation in patients with systemic mastocytosis.
abstract: OBJECTIVE
  As disruption of epigenetic control is a frequent event in solid tumors and leukemia, we investigated changes in DNA methylation (5mC) and hydroxymethylation (5hmC) in patients with systemic mastocytosis (SM), a rare myeloproliferative disease with a wide spectrum of severity, characterized by the accumulation of mast cells in various organs.
  
  
  METHODS
  We measured overall genomic levels of 5hmC and 5mC in patients with SM by dot blot, as well as by quantitative immunofluorescence in samples of cutaneous mastocytosis.
  
  
  RESULTS
  Overall 5hmC levels were reduced in all patients with SM, but to a greater extent in the presence of higher D816V mutational load in the KIT oncogene, which affects prognosis and therapeutic options in these patients. Loss of 5hmC was likely due to systemic effects of SM as it did not correlate with overall mast cell burden in these patients, nor it was due to inactivating mutations of TET2 or reduced TET2 expression.
  
  
  CONCLUSIONS
  The correlation between SM diagnosis and significantly low 5hmC levels suggests that reduction of 5hmC represents a systemic effect of SM that may be useful for patient stratification and that measurements of 5hmC levels may serve as a better prognostic marker than TET2 mutations.
authors: Institute for Research in Biomedicine, Universita' della Svizzera italiana (USI), Bellinzona, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors: Cristina
authors: C
authors: Leoni
authors: Institute for Research in Biomedicine, Universita' della Svizzera italiana (USI), Bellinzona, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors: Sara
authors: S
authors: Montagner
authors: Institute for Research in Biomedicine, Universita' della Svizzera italiana (USI), Bellinzona, Switzerland.
authors: Lorenzo
authors: L
authors: Deho'
authors: Institute for Research in Biomedicine, Universita' della Svizzera italiana (USI), Bellinzona, Switzerland.
authors: Rocco
authors: R
authors: D'Antuono
authors: Section of Clinical Biochemistry, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors: Giovanna
authors: G
authors: De Matteis
authors: Dipartimento di Fisiopatologia Medico-Chirurgica e dei Trapianti, Università degli Studi di Milano, Unità Operativa di Dermatologia, IRCCS Fondazione Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
authors: Angelo V
authors: AV
authors: Marzano
authors: Department of Oncology-Hematology, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors: Serena
authors: S
authors: Merante
authors: Department of Oncology-Hematology, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors: Ester M
authors: EM
authors: Orlandi
authors: Section of Hematology, Department of Medicine, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy.
authors: Roberta
authors: R
authors: Zanotti
authors: Institute for Research in Biomedicine, Universita' della Svizzera italiana (USI), Bellinzona, Switzerland.
authors: Silvia
authors: S
authors: Monticelli
mesh_terms: D001706:Biopsy; D001853:Bone Marrow / Q000473:pathology; D002460:Cell Line; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology; D034721:Mastocytosis, Systemic / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: 5-hydroxymethylation; DNA methylation; TET2; epigenetics; systemic mastocytosis