title: Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia.
abstract: The myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal haematological diseases characterized by ineffective haematopoiesis and predisposition to acute myeloid leukaemia (AML). The pathophysiology of MDSs remains unclear. A definition of the molecular biology of MDSs may lead to a better classification, new prognosis indicators and new treatments. We studied a series of 40 MDS/AML samples by high-density array-comparative genome hybridization (aCGH). The genome of MDSs displayed a few alterations that can point to candidate genes, which potentially regulate histone modifications and WNT pathways (e.g. ASXL1, ASXL2, UTX, CXXC4, CXXC5, TET2, TET3). To validate some of these candidates we studied the sequence of ASXL1. We found mutations in the ASXL1 gene in four out of 35 MDS patients (11%). To extend these results we searched for mutations of ASXL1 in a series of chronic myelomonocytic leukaemias, a disease classified as MDS/Myeloproliferative disorder, and found mutations in 17 out of 39 patients (43%). These results show that ASXL1 might play the role of a tumour suppressor in myeloid malignancies.
authors.affiliation: Centre de Recherche en Cancérologie de Marseille, Département d'Oncologie Moléculaire, UMR891 Inserm, Institut Paoli-Calmettes, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gelsi-Boyer
authors.forename: Virginie
authors.initials: V
authors.lastname: Trouplin
authors.forename: José
authors.initials: J
authors.lastname: Adélaïde
authors.forename: Julien
authors.initials: J
authors.lastname: Bonansea
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cervera
authors.forename: Nadine
authors.initials: N
authors.lastname: Carbuccia
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lagarde
authors.forename: Thomas
authors.initials: T
authors.lastname: Prebet
authors.forename: Meyer
authors.initials: M
authors.lastname: Nezri
authors.forename: Danielle
authors.initials: D
authors.lastname: Sainty
authors.forename: Sylviane
authors.initials: S
authors.lastname: Olschwang
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.forename: Max
authors.initials: M
authors.lastname: Chaffanet
authors.forename: Marie-Joëlle
authors.initials: MJ
authors.lastname: Mozziconacci
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002889:Chromosomes, Human, Pair 2; D041321:Chromosomes, Human, X; D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C473949:ASXL1 protein, human; D012097:Repressor Proteins