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New Program Highlights: The CTD² Network and CGCI

The Cancer Target Discovery and Development (CTD2)

NCI's Cancer Target Discovery and Development (C-T-D-Squared) Program

The Cancer Target Discovery and Development (CTD^2) Network is a collaborative functional genomics research program aiming to bridge the knowledge gap between genomic data and understanding of cancer.

CCG's Office of Cancer Genomics (OCG) manages a diverse portfolio of initiatives that aim to enhance our understanding of the molecular mechanisms of cancer. Ultimately the goal of each of these programs is to improve the lives and outcomes of cancer patients, and where possible, prevent cancer before it becomes a tumor. The Cancer Target Discovery and Development (CTD²) Network is one of these important initiatives. A recent investment from the Recovery Act spurred the formation of this five-team network of investigators who will leverage their respective expertise to accelerate the research pipeline from multi-dimensional cancer genomics datasets to target discovery and biological validation.

Why is now the right time?

Investigators in the CTD² Network agree that now is the perfect time to optimize such a pipeline. Programs like The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the Cancer Genome Characterization Initiative (CGCI) are assembling the “parts lists” of different cancers. TCGA is developing a catalog of all the genomic changes in at least 20 different cancer types. Already, copy number data, alterations in miRNA and gene expression, changes in methylation, and targeted and whole genome sequencing have been completed in hundreds of ovarian serous cystadenocarcinoma and glioblastoma samples. At the same time, analytical approaches to interrogate this data are also rapidly improving. This convergence of data and bioinformatics makes the present the right time for this network approach.

The CTD² Network brings together some of the world's leading experts in high-throughput small molecule and RNAi screening, animal modeling, and computational modeling. Over the next two years, the five CTD² projects will provide standardized protocols and data to the entire cancer research community.

The following groups have been selected as molecular CTD² Centers:

Organization Project Title Principal Investigator
Broad Institute, Cambridge, MA Targeting Causal Cancer Genes with Small Molecules Stuart Schreiber, Ph.D.
Cold Spring Harbor Laboratory, Long Island, NY Cold Spring Harbor Laboratory Molecular Target Discovery and Development Center Scott Powers, Ph.D.
Columbia University, New York, NY Systems Biology of Tumor Progression and Drug Resistance Andrea Califano, Ph.D.
Dana Farber Cancer Institute, Boston, MA Functional Annotation of Cancer Genomes: TCGA, Glioblastoma and Ovarian Cancer William Hahn, M.D., Ph.D., Lynda Chin, M.D., and Ronald DePinho, M.D.
University of Texas Southwestern Medical Center, Dallas, TX A Concerted Attack on Patient Specific Oncogenic Vulnerabilities in Lung Cancer Michael Roth, Ph.D.

New Program Highlight: Cancer Genome Characterization Initiative

The Cancer Genome Characterization Initiative (CGCI)

The Cancer Genome Characterization Initiative (CGCI) characterizes pediatric and rare adult cancers.

The Cancer Genome Characterization Initiative (CGCI) is another program in OCG's portfolio that is actively applying genomic technologies to human cancers. Currently CGCI is focusing on medulloblastoma primarily in pediatric cases and diffuse large B-cell lymphoma (DLBCL) in adults.

Medulloblastoma is the most common malignant brain tumor of childhood, accounting for approximately 20 percent of pediatric brain tumor diagnoses. Investigators at Johns Hopkins University are sequencing more than 20,000 genes (the protein coding exome from Ensembl, RefSeq, and CCDS databases) in 23 cases in the discovery phase. The data were submitted to the National Center for Biotechnology Information (NCBI) trace archive. The next phase of the project will include the validation of the mutated genes and estimation of mutation frequencies in a larger number of cases.

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin lymphoma. The Genome Sciences Centre at the British Columbia Cancer Agency has recently released data on 51 cases of DLBCL and follicular lymphoma. These data are allowing investigators to discover mutations in expressed genes and evidence of other genomic alterations including, but not limited to, translocations, insertions, and deletions. Most recently, CGCI researchers discovered a subset of lymphoma with somatic mutations in EZH2 proteins. The research (Morin, Johnson, Severson, et al, 2010), published in January in Nature Genetics, also demonstrated that altered EZH2 proteins, corresponding to the most frequent mutations found in human lymphomas, have reduced activity using in vitro histone methylation assays. Controlled access data is available to approved users who apply through an official data access request.

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Director's Note - July 2010

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