title: High-resolution single-nucleotide polymorphism array-profiling in myeloproliferative neoplasms identifies novel genomic aberrations.
abstract: Single-nucleotide polymorphism arrays allow for genome-wide profiling of copy-number alterations and copy-neutral runs of homozygosity at high resolution. To identify novel genetic lesions in myeloproliferative neoplasms, a large series of 151 clinically well characterized patients was analyzed in our study. Copy-number alterations were rare in essential thrombocythemia and polycythemia vera. In contrast, approximately one third of myelofibrosis patients exhibited small genomic losses (less than 5 Mb). In 2 secondary myelofibrosis cases the tumor suppressor gene NF1 in 17q11.2 was affected. Sequencing analyses revealed a mutation in the remaining NF1 allele of one patient. In terms of copy-neutral aberrations, no chromosomes other than 9p were recurrently affected. In conclusion, novel genomic aberrations were identified in our study, in particular in patients with myelofibrosis. Further analyses on single-gene level are necessary to uncover the mechanisms that are involved in the pathogenesis of myeloproliferative neoplasms.
authors.affiliation: Department of Internal Medicine III, University Hospital of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Stegelmann
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Martin
authors.initials: M
authors.lastname: Griesshammer
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Holzmann
authors.forename: Marianne
authors.initials: M
authors.lastname: Habdank
authors.forename: Susanne
authors.initials: S
authors.lastname: Kuhn
authors.forename: Carmen
authors.initials: C
authors.lastname: Maile
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schauer
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
mesh_terms: D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000235:genetics; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics*; D009456:Neurofibromatosis 1 / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2