CCG and the offices it oversees—The Cancer Genome Atlas (TCGA) and the Office of Cancer Genomics (OCG)—manage multiple programs. These offices serve to advance CCG's goal of ushering in a modern era of diagnosis, treatment, and prevention based on the study of genomes.
Genomic Data Commons (GDC)
CCG has established the NCI Genomic Data Commons (GDC) as a unified knowledge base that integrates and stores the diverse datasets from CCG’s programs as well as data from independent submitters. The GDC is an interactive platform for expanded data deposition, standardization, and access. Initially, the GDC houses data from:
- The Cancer Genome Atlas (TCGA)
- Therapeutically Applicable Research to Generate Effective Treatments (TARGET)
The GDC facilitates investigation of its high quality genomic data by enabling users to repeatedly mine the data and combine it with data from their own research or from third parties. The GDC is being built and managed by the University of Chicago, in collaboration with Ontario Institute for Cancer Research, through a subcontract with Leidos.
Cancer Driver Discovery Program (CDDP)
CDDP aims to identify driver mutations in as few as 2% of patients. Further elucidation of the molecular causes of cancer through deeper characterization of tumors is expected to yield insights into tumor biology, leading to better treatment options. Although a large number of driver mutations have been identified through the efforts of TCGA, some tumor types have not been characterized deeply enough to reach that level of discovery. By sequencing larger numbers of cases, CDDP will have the statistical power to discover recurrent mutations in genes that may drive the oncogenic process.
CDDP selected cancers to be analyzed based on statistical models that suggest additional driver mutations remain to be discovered, while also considering the public health impact of further research into these cancers. As a pilot project, CDDP will analyze samples from lung, colon, and ovarian cancers, and all data will be shared through the Genomic Data Commons (GDC).
Tracking Cancer Evolution through Treatment (TRACERx):
CCG is partnering with Cancer Research UK’s TRACERx study to better understand lung cancer outcomes through genomics. Launched in 2013, TRACERx, tracks the disease of 850 patients with lung adenocarcinoma over the course of their treatment, including when some patients tragically relapse following treatment. The goals of the study are to understand how intratumoral heterogeneity, diversity within a tumor, affects clinical outcomes, and to establish the impact of particular lung cancer treatments on tumors. TRACERx collaborators in the UK are analyzing the exomes, the areas of the genome that encode proteins, of the 850 patients at a deep enough level to measure intratumoral heterogeneity. Other collaborators in the UK will analyze the involvement of immune cells in the tumors as well as circulating cells and DNA in blood samples. CCG will contribute whole genome sequencing and total RNA sequencing to the TRACERx study. By providing information about the areas of the genome that do not code for proteins but impact cells in other ways, and the sequence and expression of RNA, CCG’s data will provide a clearer portrait of the cancer genomes and help TRACERx realize its goals.
Target Lung Cancer: CCG is characterizing the genomes of patients who donated tissues to the St. James’s Hospital Foundation Lung Cancer Biobank as part of the Target Lung Cancer project. Established in 2004, St. James’s Hospital Biobank collects and maintains tumor tissues and associated follow-up information, including patients’ treatments and long-term survival. St. James’s Hospital is providing 600 tissue samples that each have at least three years of follow-up data, and CCG will perform a suite of genomic analyses, including DNA sequencing of whole genomes as well as exomes, the areas of the genome that encode proteins, and total RNA sequencing. CCG will combine this comprehensive genomic characterization with clinical information to identify rare driver events and better understand patient responses.
N0147 Clinical Trial of Colon Cancer: NCI-funded clinical trial N0147, run by the North Central Cancer Treatment Group, will provide CCG with 1,400 biospecimens from its Phase III trial testing the addition of cetuximab to the treatment of patients with Stage III Colon Cancer. The trial randomly assigned qualifying patients to one of two treatment arms: a modified version of a chemotherapy regimen called FOLFOX, or the same FOLFOX regimen plus cetuximab, an antibody that binds to epidermal growth factor receptor (EGFR) to mitigate abnormal growth. The trial’s aim to evaluate the effectiveness of cetuximab in combination with chemotherapy will be extended to a deeper understanding of the patient outcomes and a broader study of cancer genomics by CCG’s genomic analysis pipeline. CCG will provide information on DNA sequence, RNA sequence and expression, variations in the number of copies of genes, chemical markers added to DNA called methylation, and proteins, the molecular machines of the cell. Characterizing all of these genomic modalities within the context of clinical trial N0147 will allow CCG to identify molecular attributes associated with patient responses and contribute to a greater understanding of colon cancer.
Cancer Genome Characterization Initiative (CGCI)
CGCI supports cutting-edge genomics research to inform better diagnosis and treatment of adult and pediatric cancers. CGCI researchers develop and apply advanced sequencing and other characterization methods to identify novel genomic abnormalities in tumors. The HIV+ Tumor Molecular Characterization Project (HTMCP) and Burkitt Lymphoma Genome Sequencing Project (BLGSP) are two active CGCI projects. HTMCP aims to reveal potentially causative mutations that may respond to novel therapies through the molecular characterization of three selected cancer types from HIV-positive patients. BLGSP is characterizing genomic abnormalities in three subtypes of Burkitt lymphoma to find diagnostic, prognostic, or therapeutic markers.
Cancer Target Discovery and Development Network (CTD2)
CTD2 develops and applies new approaches to accelerate the translation of genomic discoveries into novel treatments and clinical biomarkers. CTD2 is a collaborative network of laboratories with complementary and unique technical expertise in areas such as bioinformatics, genome-wide functional screening, protein-protein interaction identification, and small molecule high-throughput screening. These technologies allow the CTD2 Network to functionally validate potential cancer targets that may be clinically actionable upon further investigation.
Human Cancer Models Initiative (HCMI)
HCMI is an international collaboration between the NCI, Cancer Research UK, the Wellcome Trust Sanger Institute, and the foundation Hubrecht Organoid Technology whose goal is to generate a publically available bank of 1,000 next-generation cancer models. HCMI addresses problems with current cancer cell lines by utilizing new, innovative technologies, including organoid and conditionally reprogrammed cell (CRC) culturing techniques, to create cancer models that more accurately represent the architecture and complexity of real tumors. These models will also have their associated genomic data and clinical data characterized and made available to the research community. Because of HCMI’s advanced methods and comprehensive associated data, these models will provide researchers with better tools for their cell culture experiments and enable discoveries that more closely mirror the biology of cancer. In the future, patient-derived models like those generated by HCMI may also become an important tool for precision oncology, as they may be developed to accurately predict of the most effective therapies for patients.
Therapeutically Applicable Research to Generate Effective Treatments (TARGET)
TARGET applies comprehensive genomic approaches to determine molecular changes that drive certain childhood cancers. These cancers include the aggressive and hard to treat subsets of acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, osteosarcoma, and several types of kidney tumors. TARGET aims to identify prognostic markers and therapeutic targets from molecular profile data of each tumor type to develop more effective, less toxic clinical strategies. TARGET investigators participate in a collaborative research network that includes the NCI-supported Children's Oncology Group and NCI's Cancer Therapy Evaluation Program (CTEP). This clinically integrated network facilitates discovery of molecular targets and the rapid translation of those findings to the clinic.
The Cancer Genome Atlas (TCGA)
TCGA is a comprehensive and coordinated effort to accelerate the cancer research community’s understanding of the molecular basis of cancer. The program applied large-scale genome analysis technologies to 33 cancer types, including ten rare cancers. TCGA's data is freely available to the entire cancer research community. TCGA is a joint effort of NCI and the National Human Genome Research Institute (NHGRI), both of which are part of the National Institutes of Health (NIH).