e22139 Background: Myeloproliferative neoplasms (MPNs) are a heterogeneous group of tumors marked by clonal proliferation of myeloid cells with variable marrow changes and clinical findings. Though progress has been made since the discovery of the JAK2V617F mutation, few data exist on the genetic distinction amongst these disorders, or pathogenesis of fibrosis seen in MPNs. Methods: Array-based comparative genomic hybridization (aCGH) was performed on genomic DNA extracted from marrow aspirate using an Agilent 180K oligonucleotide array platform in order to discover recurrent genetic aberrations, cooperating mutations, and gain insight into the hierarchy of molecular pathogenesis of fibrosis. BM aspirate from 17 pts were analyzed. Copy number alterations (CNAs) were compared to a reference set and mapped to functional genes. Genes with CNA were subjected to gene ontology, pathway and clustering analysis. Results: aCGH yielded copy number gains or losses in 17 out of 17 cases, 11 of which had normal karyotype and/or FISH. Numerous CNAs were identified within genes found in a variety of cellular pathways. In particular, alterations in COL1A1, NFKb and PDGFRb were implicated in this MPN cohort in 12, 8, and 6, pts, respectively. Interestingly, only patients with COL1A1 CNA had aberrancy within NFKb and PDGFRb. The remaining 5 pts had abnormal aCGH, but normal signals at these 3 genes. Conclusions: aCGH is a valuable tool which may be used to distinguish MPNs, particularly when standard testing does not. The presence of the COL1A1 aberration in 12/17 cases edifies evolving study of the role of TGFB superfamily in development of fibrosis and provides potential targets to exploit in the treatment of MPNs. Though aberrations within COL1A1 have not been previously reported in MPNs, a gene fusion involving COL1A1 and PDGFRb is found in 90% of dermatofibrosarcoma protuberans. The cooperation between these genes is currently under study in a larger cohort of pts with MPNs. [Table: see text]
Clinicopathological features and global genomic copy number alterations of pilomyxoid astrocytoma in the hypothalamus/optic pathway: comparative analysis with pilocytic astrocytoma using array-based comparative genomic hybridization