High-resolution single-nucleotide polymorphism array-profiling in myeloproliferative neoplasms identifies novel genomic aberrations.
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.
Stegelmann
Frank
F
Department of Internal Medicine III, University Hospital of Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Bullinger
Lars
L
Griesshammer
Martin
M
Holzmann
Karlheinz
K
Habdank
Marianne
M
Kuhn
Susanne
S
Maile
Carmen
C
Schauer
Stefanie
S
Döhner
Hartmut
H
Döhner
Konstanze
K
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*
C507924:JAK2 protein, human; D053614:Janus Kinase 2