title: SNPs array karyotyping reveals a novel recurrent 20p13 amplification in primary myelofibrosis.
abstract: The molecular pathogenesis of primary mielofibrosis (PMF) is still largely unknown. Recently, single-nucleotide polymorphism arrays (SNP-A) allowed for genome-wide profiling of copy-number alterations and acquired uniparental disomy (aUPD) at high-resolution. In this study we analyzed 20 PMF patients using the Genome-Wide Human SNP Array 6.0 in order to identify novel recurrent genomic abnormalities. We observed a complex karyotype in all cases, detecting all the previously reported lesions (del(5q), del(20q), del(13q), +8, aUPD at 9p24 and abnormalities on chromosome 1). In addition, we identified several novel cryptic lesions. In particular, we found a recurrent alteration involving cytoband 20p13 in 55% of patients. We defined a minimal affected region (MAR), an amplification of 9,911 base-pair (bp) overlapping the SIRPB1 gene locus. Noteworthy, by extending the analysis to the adjacent areas, the cytoband was overall affected in 95% of cases. Remarkably, these results were confirmed by real-time PCR and validated in silico in a large independent series of myeloproliferative diseases. Finally, by immunohistochemistry we found that SIRPB1 was over-expressed in the bone marrow of PMF patients carrying 20p13 amplification. In conclusion, we identified a novel highly recurrent genomic lesion in PMF patients, which definitely warrant further functional and clinical characterization.
authors: Hematology and Hematopoietic Stem Cell Transplant Center, San Salvatore Hospital, Pesaro, Italy.
authors: Giuseppe
authors: G
authors: Visani
authors: Maria Rosaria
authors: MR
authors: Sapienza
authors: Alessandro
authors: A
authors: Isidori
authors: Claudio
authors: C
authors: Tripodo
authors: Maria Antonella
authors: MA
authors: Laginestra
authors: Simona
authors: S
authors: Righi
authors: Carlo A
authors: CA
authors: Sagramoso Sacchetti
authors: Anna
authors: A
authors: Gazzola
authors: Claudia
authors: C
authors: Mannu
authors: Maura
authors: M
authors: Rossi
authors: Michele
authors: M
authors: De Nictolis
authors: Massimo
authors: M
authors: Valentini
authors: Meris
authors: M
authors: Donati
authors: Roberto
authors: R
authors: Emiliani
authors: Francesco
authors: F
authors: Alesiani
authors: Stefania
authors: S
authors: Paolini
authors: Carlo
authors: C
authors: Finelli
authors: Stefano A
authors: SA
authors: Pileri
authors: Pier Paolo
authors: PP
authors: Piccaluga
mesh_terms: D000368:Aged; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D023281:Genomics; D006801:Humans; D007621:Karyotyping; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055728:Primary Myelofibrosis / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D019914:Taq Polymerase / Q000378:metabolism; D024182:Uniparental Disomy / Q000235:genetics
chemical_list: D011956:Receptors, Cell Surface; C501921:SIRPB1 protein, human; D004247:DNA; D019914:Taq Polymerase