High-resolution SNP-array profiling in myeloproliferative neoplasms

SNP arrays allow for genome-wide profiling of copy-number alterations (CNAs) and copy-neutral runs of homozygosity (ROH) at high resolution. To identify novel genetic lesions in myeloproliferative neoplasms (MPN), a large series of 151 clinically well-characterized patients was analyzed in our study. CNAs were rare in essential thrombocythemia and polycythemia vera. In contrast, approximately one third of myelofibrosis patients exhibited small genomic losses (< 5 Mb). In two 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 ROH, no chromosomes other than 9p were recurrently affected. In conclusion, in our study we identified novel genomic aberrations in MPN, 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 MPN. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic peripheral blood samples. Copy number analysis of Affymetrix 250K SNP arrays was performed for 151 myeloproliferative neoplasm samples [essential thrombocythemia, n=45; polycythemia vera, n=45; secondary myelofibrosis, n=14; primary myelofibrosis, n=47]. There are also 60 samples from acute myeloid leukemia patients in remission which were used as references for unpaired analysis.