SNPs array karyotyping reveals recurrent lesions in primary myelofibrosis

The molecular pathogenesis of primary mielofibrosis (PMF) is still largely unknown. Recently, single-nucleotide polymorphism arrays (SNP-A) were shown to allow for genome-wide profiling of copy-number alterations and copy-neutral runs of homozygosity (aUPD) at high resolution. In this study we performed SNP-A analysis of primary myelofibrosis, aiming to identify novel recurrent genomic abnormalities, We analyzed DNA of 20 PMF patients using the Affymetrix Genome-Wide Human SNP Array 6.0 and conventional bioinformatic tools. Validation was carried on by TaqMan Copy Number Assay and Immunoistochemistry. We observed a highly complex karyotype in all cases, detecting all the previously reported alterations (including del 20q, del13q, aUPD of 9p24, aUPD on chromosome 11 and abnormalities on chromosome 1). In addition, we identified several novel cryptic lesions. Remarkable, in overall 95% of cases, we found the 20p13 cytoband affected by lesions. Among them we defined a minimal affected region (MAR), a recurrent lesion occurring in 55% of patients. In particular, the MAR is a genomic amplification extending for 9,911 bps and overlapping the SIPB1 gene locus. These results were confirmed by real-time PCR and validated in silico in an independent series of myeloproliferative diseases. Furthermore, by immunohistochemistry assay, we assessed a consistent deregulation of the SIRPB1 protein which was high up-regulated in PMF patients carrying the amplification. In conclusion, we found a novel highly recurrent genomic lesion in PMF patients responsible of the aberrant proliferation of the encoded protein.