| Questions from Scientists

1. What is The Cancer Genome Atlas (TCGA)?
2. Why are the National Cancer Institute (NCI) and National Human Genome Research Institute (NHGRI) pursuing the characterization of the human cancer genome now?
3. What were some lessons learned during the TCGA pilot project that are being applied to the TCGA program?
4. What sort of genomic changes are being examined by the TCGA Research Network?
5. What impact will TCGA have on other cancer research?
6. How can I become a part of TCGA?
7. What are TCGA’s major challenges?
8. What cancer types are being studied as part of TCGA and how were they selected?
9. Where can I get more information?

1. What is The Cancer Genome Atlas (TCGA)?
   TCGA is a large-scale collaborative effort supported by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to systematically characterize the genomic changes that occur in cancer.
   
   Back to Top
   
   
2. Why are NCI and NHGRI pursuing the characterization of the human cancer genome now?
   At least three important advances suggest that now is the ideal time to launch a major human cancer genome effort. First, recent identification of genetic mutations linked to breast cancer, colon cancer and many other cancers has led to the development of diagnostic tests that can point to the most effective treatment or prevention strategy. This has provided the “proof of concept” that comprehensive knowledge of the molecular origins of cancer can lead to more effective diagnosis, treatment and prevention.
   
   The second major advance is the availability of the human genome sequence generated by the Human Genome Project and a map of human genetic variation completed by the International HapMap Consortium. These reference data sets provide an excellent starting point to compare genomic data derived from various cancers.
   
   Finally, technologies to sequence and analyze the genome have evolved rapidly. At the beginning of the Human Genome Project in 1990, the cost of sequencing was more than $10 per finished “letter,” or base, of the DNA code. Today, $10 in a large-scale genome center can translate to many thousands of finished DNA bases. Other high-throughput technologies for identifying genomic and epigenomic changes in the cancer cell have also recently been developed. TCGA is building upon these advances and continues to be a driving force for the development and improvement of genomic sequencing and analysis technologies.
   
   Together, these developments now make it possible for TCGA to catalog the genomic changes associated with many known forms of cancer.
   
   Back to Top
   
   
3. What were some lessons learned during the TCGA pilot project that are being applied to the TCGA program?
   In 2009, NCI and NHGRI announced the expansion of TCGA. TCGA aims to characterize more than 10,000 tumors across at least 20 tumor types by 2015. It also will implement improved procedures based on lessons learned from the pilot project. For example:
   
   
   1. Combination of Retrospective and Prospective Sample Collection: TCGA will begin working with a variety of hospitals around the country to prospectively collect samples that meet the needs of the program in addition to continuing to collect retrospective samples (samples that have already been collected and stored in tissue banks)
   2. Genome Data Analysis Centers: NCI is investing in multiple Genome Data Analysis Centers (GDACs) that will coordinate systematic, integrated and clinically relevant analysis for the program
   
   Back to Top
   
   
4. What sort of genomic changes are being examined by the TCGA Research Network?
   RNA and DNA from the same set of tumor and matched normal samples are analyzed by multiple characterization centers for copy number variation, chromosomal segment aberrations, loss of heterozygosity, epigenetic alterations, gene and miRNA expression changes as well as mutation by large-scale sequencing. A summary of the TCGA Research Network’s components provides more detail on how each laboratory is contributing to the comprehensive characterization and analysis in the TCGA program.
   
   Back to Top
   
   
5. What impact will TCGA have on other cancer research?
   NIH is committed to curing cancer. To accomplish this goal, NCI and NHGRI are putting valuable data into the hands of the global research community. The TCGA Research Network is actively depositing comprehensive data sets into publicly accessible databases. Any researcher can leverage these data to generate and/or test hypotheses, validate their own work or add power to another data set. A list of some of the scientific publications that have used the TCGA data set reveals the breadth of work enabled by TCGA. These publications represent just the first steps in yielding positive changes based on cancer genomics for clinicians and their patients.
   
   Back to Top
   
   
6. How can I become a part of TCGA?
   The researchers involved in the TCGA Research Network were selected through the NIH’s competitive, peer-reviewed Request for Applications (RFA) process. While these research teams are the primary data contributors to the TCGA data sets, the TCGA Research Network posts all data to the TCGA Data Portal for anyone to access and analyze for cancer research.
   
   We encourage all investigators involved in cancer genomics research to:
   • access the TCGA Data Portal and learn about the tools we and our collaborators have developed to analyze the valuable TCGA data sets
   • leverage the publicly available data for your own work
   • utilize open source caBIG-compatible computational tools to maximize efficiency and integration
   • make your data publicly available to enrich the entire set of data available to the research community through different sources
   • identify tissue sources (e.g. retrospective tumor collections) that may be useful to this work
   
   Back to Top
   
   
7. What are TCGA’s major challenges?
   A major challenge for cancer research, especially for the molecular characterizations of cancer-associated changes, is the complexity of the disease — cancer is actually more than 200 diseases. Different cancer types originate from a wide range of genetic mutations and molecular mechanisms. A single cancer subtype can exhibit unique genomic characteristics through several stages of its progression, from pre-cancerous lesions to metastasis.
   
   Any effort to understand cancer genomes in a comprehensive, systematic manner also must address the technological hurdles of characterizing such a heterogeneous disease. The technological challenges include the need to:
   • improve molecular characterization methods, e.g., determining which genes are expressed at different levels in tumor cells compared with normal cells or how chromosomes are rearranged in tumor cells
   • improve the throughput of these methods
   • further decrease the cost of DNA sequencing
   • improve the detection of epigenomic changes
   • develop new analytical methods to correlate disease state with the molecular characteristics of a cancer
   
   The bioinformatics challenges involve developing the best ways to collect, store and distribute the clinical and genomic data generated by the program. Among the issues that need to be considered are:
   • developing data standards and a uniform vocabulary for each new technology
   • establishing an informatics pipeline connecting all components of the program
   • creating portals for basic and clinical researchers around the world to easily access TCGA data
   • ensuring that the confidentiality of clinical data is maintained
   
   Ethical, legal and social issues facing the TCGA include:
   • ensuring that important clinical data are linked to each biospecimen
   • developing policies for data release, intellectual property protection and informed consent from biospecimen donors
   
   Back to Top
   
   
8. What cancer types are being studied as part of TCGA, and how were they selected?
   The TCGA program will expand to more than 20 tumor types over the next several years, beginning with the addition of breast and kidney cancer.
   
   In fall of 2005, NCI issued a Human Cancer Biospecimen Collection Request for Information (RFI) to identify existing biospecimen collections that may be suitable for the TCGA program. NCI and NHGRI program management staff evaluated responses to the RFI from biorepositories on the basis of various criteria, such as biospecimen quality and quantity. Staff consulted with the TCGA External Scientific Committee, a group of scientists, clinicians, patient advocates and ethicists. After consulting the data collected from the RFI and the advice of experts, three tumors were selected for the pilot project: glioblastoma multiforme (GBM, a type of brain cancer), ovarian cancer (serous cystadenocarcinoma) and squamous cell lung cancer. Biospecimens that best matched these criteria were then selected based on additional characteristics, such as which tumor types were most likely to yield genomic data that has the broadest clinical impact. The Cancer Genome Atlas Biospecimen Selection Process describes the procedures by which the TCGA is selecting tumor and healthy control biospecimens for the Biospecimen Core Resource.
   
   More information on the cancers selected for study is available on the TCGA Web site.
   
   Back to Top
   
   
9. Where can I get more information?
   For more information about TCGA, please visit the TCGA Web site at http://cancergenome.nih.gov.
   
   For more information about cancer, visit the NCI Web site at http://www.cancer.gov or call NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
   
   For more information about genetics and genomics, visit the NHGRI Web site at http://www.genome.gov.
   
   Back to Top