Genetic profiling of myeloproliferative disorders by single-nucleotide polymorphism oligonucleotide microarray.
OBJECTIVE
Myeloproliferative disorders (MPD) are clonal hematopoietic diseases that include polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). Mutations in JAK2 are present in many MPD patients. Additional genomic abnormalities are not fully examined in MPD.


METHODS
We used single-nucleotide polymorphism DNA microarray (SNP-chip) to analyze 43 patients with MPD (10 PV, 17 ET, and 16 PMF) for genomic aberrations.


RESULTS
Genomic abnormalities were rare in ET. The region containing either RB (13q14) or NF1 (17q11) was deleted in 4 of the 16 PMF, especially PMF with no JAK2 mutations. All five cases of PV having homozygous JAK2V617F had loss of heterozygosity with normal copy number [uniparental disomy] involving the gene. A subpopulation with 9p uniparental disomy was detected in 11 MPD (3 PV, 1 ET, 7 PMF). Uniparental disomy at 1p was found in one PV and three PMF. A novel mutation of MPL (Y591D), which was involved in this uniparental disomy, was found in 1 PV with JAK2 mutation. The other three cases of PMF with 1p uniparental disomy had point mutations of the MPL gene, either a novel mutation (S204F) or the previously described W515L.


CONCLUSIONS
Genomic abnormalities, including 9p uniparental disomy/JAK2 point mutations, 1p uniparental disomy/MPL point mutations, deletions of RB1 and NF1 are common alterations in MPD, especially in PMF.
Kawamata
Norihiko
N
Hematology/Oncology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, CA 90048, USA. kawamatan@cshs.org
Ogawa
Seishi
S
Yamamoto
Go
G
Lehmann
Soren
S
Levine
Ross L
RL
Pikman
Yana
Y
Nannya
Yasuhito
Y
Sanada
Masashi
M
Miller
Carl W
CW
Gilliland
D Gary
DG
Koeffler
H Phillip
HP
D002872:Chromosome Deletion; D020869:Gene Expression Profiling; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D017354:Point Mutation; D011087:Polycythemia Vera / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D055728:Primary Myelofibrosis / Q000235:genetics; D053628:Receptors, Thrombopoietin / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000235:genetics
D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2