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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA155258-03
Application #
8566976
Study Section
Special Emphasis Panel (ZCA1-RPRB-J)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
3
Fiscal Year
2013
Total Cost
$235,548
Indirect Cost
$60,775
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Fulciniti, Mariateresa; Martinez-Lopez, Joaquin; Senapedis, William et al. (2017) Functional role and therapeutic targeting of p21-activated kinase 4 in multiple myeloma. Blood 129:2233-2245
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 22:4350-4355
Ohguchi, Hiroto; Hideshima, Teru; Bhasin, Manoj K et al. (2016) The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival. Nat Commun 7:10258
Stroopinsky, Dina; Kufe, Donald; Avigan, David (2016) MUC1 in hematological malignancies. Leuk Lymphoma 57:2489-98
Richardson, Paul G; Hungria, Vânia T M; Yoon, Sung-Soo et al. (2016) Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood 127:713-21
Fulciniti, M; Amodio, N; Bandi, R L et al. (2016) miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth. Blood Cancer J 6:e380
Szalat, Raphael; Avet-Loiseau, Herve; Munshi, Nikhil C (2016) Gene Expression Profiles in Myeloma: Ready for the Real World? Clin Cancer Res 22:5434-5442
Amodio, Nicola; Stamato, Maria Angelica; Gullà, Anna Maria et al. (2016) Therapeutic Targeting of miR-29b/HDAC4 Epigenetic Loop in Multiple Myeloma. Mol Cancer Ther 15:1364-75
Xu, Lian; Hunter, Zachary R; Tsakmaklis, Nicholas et al. (2016) Clonal architecture of CXCR4 WHIM-like mutations in Waldenström Macroglobulinaemia. Br J Haematol 172:735-44
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

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