Project description:Here we characterized a series of cases with myeloid neoplasms using cytogenetic, single nucleotide polymorphism array, and next generation sequencing.
Project description:The EBF1-PDGFRB gene fusion accounts for <1% B-cell precursor acute lymphoblastic leukaemia and occurs within the Philadelphia-like ALL subtype. We performed Affymetrix SNP 6.0 array was undertaken patients who tested positive for EBF1-PDGFRB rearrangement by FISH and/or RT-PCR.
Project description:The EBF1-PDGFRB gene fusion accounts for <1% B-cell precursor acute lymphoblastic leukaemia and occurs within the Philadelphia-like ALL subtype. We performed Affymetrix SNP 6.0 array was undertaken patients who tested positive for EBF1-PDGFRB rearrangement by FISH and/or RT-PCR. We performed Affymetrix SNP 6.0 array on genomic DNA extracted from bone marrow samples taken at diagnosis in 9 patients, at relapse in one patient and at remission in one patient.
Project description:Here we characterized a series of 14 cases with myeloid neoplasms using cytogenetic, single nucleotide polymorphism array, and next generation sequencing.
Project description:Abnormalities of chromosome 7q are common in myeloid malignancies but no specific target genes have been identified. Here we describe the finding of homozygous EZH2 mutations in 9 of 12 cases with 7q acquired uniparental disomy. Screening of a total of 614 cases with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals, most commonly myelodysplastic/myeloproliferative neoplasms (27/219; 12%) and myelofibrosis (4/30; 13%). EZH2 encodes the catalytic subunit of the Polycomb repressive complex 2 (PRC2), the highly conserved histone H3 lysine 27 methyltransferase that influences stem cell renewal by epigenetic repression of genes involved in cell fate decisions. EZH2 has oncogenic activity and its overexpression has been causally linked to differentiation blocks in epithelial tumors. Unexpectedly, the mutations we identified resulted in premature chain termination or direct abrogation of histone methyltransferase activity, suggesting that EZH2 acts as a tumor suppressor for myeloid malignancies.
Project description:Nanopore Sequencing for the screening of Myeloid and Lymphoid neoplasms with eosinophilia and rearrangement of PDGFRa, PDGFRb, FGFR1 or PCM1-JAK2.
Project description:In this study, to obtain a complete registry of genetic lesions in MDS and to identify novel therapeutic targets, we performed SNP array analysis and whole exome analysis for novel mutations using high-throughput sequencing technologies. In whole exome analysis, paired CD3-positive T cells were used as a normal control. By comparing sequences in tumors and paired T cells, 268 non-synonymous somatic mutations were confirmed with an overall true positive rate of 53.9 %, including 206 missense, 25 nonsense, and 10 splice site mutations, and 27 frameshift-causing insertions/deletions (indels). The mutations of the known gene targets, however, accounted for only 12.3 % of all detected mutations (N = 33), and the remaining 235 mutations involved previously unreported genes. Combined with the genomic copy number profile obtained by SNP array karyotyping, this array of somatic mutations provided a landscape of myelodysplasia genomes. Copy number analysis of Affymetrix 250K SNP arrays was performed for 29 MDS or related neoplasms and paired 29 germline samples.