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Publications (19)
The Eμ-Myc mouse is an extensively used model of MYC driven malignancy; however to date there has only been partial characterization of MYC co-operative mutations leading to spontaneous lymphomagenesis. Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. We identif...
Supplementary Figures, Supplementary Tables.
Performance statistics for whole-exome sequencing
SNVs and InDels identified from whole-exome sequencing of Eu-Myc/P19ARF-/+ lymphomas
PCR primers used for variant validation and qRT-PCR
Genes located within chr19 amplicon identified proximal to transgene insertion in Eu- Myc germline
SNVs and InDels identified from whole-exome sequencing of Eu-Myc lymphomas
Cancer genes identified within recurrent CNV regions of Eu-Myc lymphoma
BCOR gene expression signature from Eu-Myc lymphomas
Frequency of BCOR mutations identified in human in human haematological malignancies extracted from COSMIC database
Performance statistics for whole-genome sequencing
Targeting BET bromodomain proteins utilizing small molecules in an emerging anti-cancer strategy with clinical evaluation of at least six inhibitors now underway. While MYC downregulation was initially proposed as a key mechanistic property of BET inhibitors, recent evidence suggests that additional anti-tumor activities are important. Using the Eμ...
Leukemia is one of the leading journals in hematology and oncology. It is published monthly and covers all aspects of the research and treatment of leukemia and allied diseases. Studies of normal hemopoiesis are covered because of their comparative relevance.
Genetically-engineered mouse models offer controlled and reproducible systems in which to study the genetics of cancer development. We have used massively-parallel sequencing to provide a comprehensive analysis of the step-wise progression of cancer in the highly tractable Eμ-Myc mouse model. The Eμ-Myc mouse has been engineered to harbor a t(8;14)...
Multiple myeloma (MM) is an incurable malignancy with an unmet need for innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new class of anticancer agent that have demonstrated activity in hematological malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat, panobinostat, romidepsin) and novel combin...
The attrition rate for anticancer drugs entering clinical trials is unacceptably high. For multiple myeloma (MM), we postulate that this is because of preclinical models that overemphasize the antiproliferative activity of drugs, and clinical trials performed in refractory end-stage patients. We validate the Vk*MYC transgenic mouse as a faithful mo...
Introduction: Multiple myeloma (MM) is an incurable hematological neoplasm with an unmet need for novel therapeutic options. Here we employed the genetically tractable Vk*MYC murine model of MM to screen current and novel therapeutics in transgenic Vk*MYC mice and in transplant models of Vk*MYC MM. In addition to assessing single agent activity we...
Background / Purpose:
The histone-deacetylase inhibitor (HDACi) panobinostat (LBH-589) has demonstrated anticancer activities in laboratory studies and the clinic.Here we investigated the ability of panobinostat to induce apoptosis in multiple myeloma (MM) cells, and when combined with agents targeting the extrinsic apoptosis pathway (rhTRAIL) or...
