Multiple Myeloma (MM) Is a complex disease driven by numerous genetic and epigenetic alterations. Our compretiensive oncogenomic analysis indicates the presence of many tightly recurrent and tightly focal amplifications/deletions in the MM genome. Indeed, integrated oncogenomic analyses of human MM have identified candidates resident within regions of amplification/deletions predicted to be involved in MM pathogenesis and progression. Using the clinical and genomic information from patient samples, our goals are to identify novel molecular lesions with clinical prognostic and therapeutic correlation. Our preliminary oncogenomic studies have confirmed our ability to perform large-scale high-throughput genomic profiling on myeloma cells from patient bone marrow (BM) samples. We hypothesize that the biological behavior and clinical outcome in MM is dependent on molecular determinants, which are also attractive therapeutic targets. In this Project we will: characterize the spectrum of genomic lesions associated with pathogenesis and progression of monoclonal gammopathy of undetermined significance (MGUS)/Smoldering MM (SMM) to active MM (Sp Aim 1);identify genomic alterations in 1,000 newly diagnosed uniformly treated patients correlating with clinical outcome (Sp Aim 2);and determine whether mechanisms modifying transcriptome are associated with clinical outcome (Sp Aim 3). This project will provide a better understanding of the impact of copy number and gene expression alterations and their functional consequences on MM initiation and progression, as well as identify novel targets for therapeutic intervention.

Public Health Relevance

This project will identify genomic markers of progression of MGUS/SMM to myeloma and highlight alteration in copy number and gene expression predictive of prognosis in uniformly treated patients. This will also identify novel targets for validation and therapeutic application.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-J)
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Dana-Farber Cancer Institute
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Bae, J; Prabhala, R; Voskertchian, A et al. (2015) A multiepitope of XBP1, CD138 and CS1 peptides induces myeloma-specific cytotoxic T lymphocytes in T cells of smoldering myeloma patients. Leukemia 29:218-29
Hu, Y; Song, W; Cirstea, D et al. (2015) CSNK1?1 mediates malignant plasma cell survival. Leukemia 29:474-82
Moreau, Philippe; Cavo, Michele; Sonneveld, Pieter et al. (2014) Combination of international scoring system 3, high lactate dehydrogenase, and t(4;14) and/or del(17p) identifies patients with multiple myeloma (MM) treated with front-line autologous stem-cell transplantation at high risk of early MM progression-related J Clin Oncol 32:2173-80
Lu, R; Pal, J; Buon, L et al. (2014) Targeting homologous recombination and telomerase in Barrett's adenocarcinoma: impact on telomere maintenance, genomic instability and tumor growth. Oncogene 33:1495-505
Anderson, K K; Flora, N; Archie, S et al. (2014) A meta-analysis of ethnic differences in pathways to care at the first episode of psychosis. Acta Psychiatr Scand 130:257-68
Chretien, Marie-Lorraine; Hebraud, Benjamin; Cances-Lauwers, Valérie et al. (2014) Age is a prognostic factor even among patients with multiple myeloma younger than 66 years treated with high-dose melphalan: the IFM experience on 2316 patients. Haematologica 99:1236-8
Samur, Mehmet Kemal (2014) RTCGAToolbox: a new tool for exporting TCGA Firehose data. PLoS One 9:e106397
Cottini, Francesca; Hideshima, Teru; Xu, Chunxiao et al. (2014) Rescue of Hippo coactivator YAP1 triggers DNA damage-induced apoptosis in hematological cancers. Nat Med 20:599-606
Hebraud, B; Leleu, X; Lauwers-Cances, V et al. (2014) Deletion of the 1p32 region is a major independent prognostic factor in young patients with myeloma: the IFM experience on 1195 patients. Leukemia 28:675-9
Cooke, Susanna L; Shlien, Adam; Marshall, John et al. (2014) Processed pseudogenes acquired somatically during cancer development. Nat Commun 5:3644

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