Whole genome sequencing is a specialized function requiring expertise, special instruments and facilities along with informatics capabilities. This function cannot be performed in individual laboratories. Whole genome sequencing is also evolving rapidly and constantly improving the read capabilities, number of samples per run and informatics capabilities. There is only limited number of facilities available worldwide with such capabilities. Welcome Trust Sanger Institute (WTSI) is a leader in sequencing the human genome, contributing one third of all the sequences and has made numerous contributions to other large genomes, Idad efforts to sequence pathogens and disease vectors and mouse Rl strain genomes. WTSI is committed to continually appraising new sequencing technologies, using in-house testing wherever possible, and will use whatever future technology is most suitable and cost-effective for the applications demanded by the science pursued at the Institute. The purpose of Core D is to provide for comprehensive genomic sequence analyses by utilizing a state of the art 'next generation'sequencing platform for both the sequencing of all coding exons/miRNA genes and the identification and characterization of genome-wide rearrangements at base-pair resolution in samples detailed in Projects 1 and 2. To meet these goals, in Core D we will pursue the following specific aims: to generate comprehensive somatic mutation data for all coding exons and miRNA genes from selected samples from patients progressing from monoclonal gammopathy of underemined significance (MGUS) smoldering multiple myeloma (SMM) to active multiple myeloma (MM) or MM evolution from diagnosis to relapse (Specific Aim 1);and to generate a genome-wide rean^angement data at base-pair resolution from selected samples to explore genomic changes during MM evolution from diagnosis to relapse (Specific Aim 2). Further, the core will provide bioinformatics expertise in the management and analysis of data produced within the core to support the projects.

Public Health Relevance

The core will perform high output whole genome sequencing, uniformly analyze clinical sample both to investigate for genomic and transcriptomic changes in MGUS vs MM and correlate changes in MM with various clinical groups.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-RPRB-J)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Dana-Farber Cancer Institute
United States
Zip Code
Gullà, Annamaria; Di Martino, Maria Teresa; Gallo Cantafio, Maria Eugenia et al. (2016) A 13 mer LNA-i-miR-221 Inhibitor Restores Drug Sensitivity in Melphalan-Refractory Multiple Myeloma Cells. Clin Cancer Res 22:1222-33
Prabhala, R H; Fulciniti, M; Pelluru, D et al. (2016) Targeting IL-17A in multiple myeloma: a potential novel therapeutic approach in myeloma. Leukemia 30:379-89
Magrangeas, Florence; Kuiper, Rowan; Avet-Loiseau, Hervé et al. (2016) A Genome-Wide Association Study Identifies a Novel Locus for Bortezomib-Induced Peripheral Neuropathy in European Patients with Multiple Myeloma. Clin Cancer Res 22:4350-5
Ohguchi, Hiroto; Hideshima, Teru; Bhasin, Manoj K et al. (2016) The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival. Nat Commun 7:10258
Dimopoulos, Meletios A; Orlowski, Robert Z; Facon, Thierry et al. (2015) Retrospective matched-pairs analysis of bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple myeloma. Haematologica 100:100-6
Bianchi, Giada; Munshi, Nikhil C (2015) Pathogenesis beyond the cancer clone(s) in multiple myeloma. Blood 125:3049-58
Jagannathan, S; Vad, N; Vallabhapurapu, S et al. (2015) MiR-29b replacement inhibits proteasomes and disrupts aggresome+autophagosome formation to enhance the antimyeloma benefit of bortezomib. Leukemia 29:727-38
Hu, Y; Song, W; Cirstea, D et al. (2015) CSNK1α1 mediates malignant plasma cell survival. Leukemia 29:474-82
Hebraud, Benjamin; Magrangeas, Florence; Cleynen, Alice et al. (2015) Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience. Blood 125:2095-100
Mitsiades, Constantine S (2015) Therapeutic landscape of carfilzomib and other modulators of the ubiquitin-proteasome pathway. J Clin Oncol 33:782-5

Showing the most recent 10 out of 161 publications