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.

SNPs array karyotyping reveals a novel recurrent 20p13 amplification in primary myelofibrosis.

SAPIENZA, MARIA ROSARIA;LAGINESTRA, MARIA ANTONELLA;RIGHI, SIMONA;SAGRAMOSO SACCHETTI, CARLO ALBERTO;GAZZOLA, ANNA;Mannu C;Rossi M;PAOLINI, STEFANIA;PILERI, STEFANO;PICCALUGA, PIER PAOLO
2011

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.
Visani G; Sapienza MR; Isidori A; Tripodo C; Laginestra MA; Righi S; Sagramoso Sacchetti CA; Gazzola A; Mannu C; Rossi M; De Nictolis M; Valentini M; Donati M; Emiliani R; Alesiani F; Paolini S; Finelli C; Pileri SA; Piccaluga PP.
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Descrizione: Figure S3: Acquired uniparental disomy (aUPD) in PMF patients
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Descrizione: Figure S4: Recurrence of CNVs across PMF patients
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Descrizione: Figure S5: Recurrence of 20p13 in a panel of myeloproliferative neoplasms
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Descrizione: File S1: All the 2,765 CNVs detected in the training set patients are reported. For each lesion is indicated the length, the chromosome , the cytoband and the genes eventually involved
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Descrizione: Table S1: Patients Characterisctics.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/122930
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