Cancer may have as many as 200 different types and even more subtypes. The Cancer Genome Atlas (TCGA) project seeks to generate a collection of comprehensive, multidimensional maps of the key genomic changes in major types and subtypes of cancer. TCGA is jointly led by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), and its research network includes 15 sites in the United States and one in Canada.
“The goal of this program is to create a reference set—a set of data that gives us an idea of the spectrum of alterations found in primary human tumors. While a large program, much is yet to be done before these discoveries make it to the clinic. TCGA’s research is laying the foundation upon which advancements in patient care can be built,” explained Kenna Shaw, PhD, Director of TCGA Program Office at NCI in an interview.
COMPREHENSIVE GENOMIC MAPS
TCGA began as a pilot study in 2006 to characterize brain tumors and ovarian cancer. It generated unprecedented amounts of data of unequaled quality, and in 2009, TCGA announced plans to produce comprehensive genomic maps of at least 20 types of cancer over the next 5 years. This effort was funded with $175 million from American Recovery and Reinvestment Act funds, along with $50 million each from both NCI and NHGRI.
TCGA is unique among sequencing projects because it uses complimentary technology platforms to perform multidimensional analyses. For example, the analyses of acute myeloid leukemia (AML) included whole-genome sequencing of the primary tumor and matched skin samples, and exome capture and sequencing of paired tumor and skin samples.1 In its analysis of breast cancer, tumor and germline samples were obtained from 825 patients. The samples were analyzed with mRNA expression microarrays, DNA methylation, single nucleotide polymorphism (SNP) arrays, microRNA (miRNA) sequencing, and whole exome sequencing, along with reverse-phase protein array data for 466 samples (Figure 1).2
“TCGA has shown that an international network of clinicians, pathologists, scientists, and disease experts can work together to generate the rich data provided at our websites (TCGA Data Portal and CGHub),” said Shaw. These website portals make the data generated by TCGA available to the public.
SAMPLE QUANTITY TO ACHIEVE QUALITY DATA
The goal is to comprehensively characterize more than 10,000 tumor and matched germline samples across more than 25 tumor types, including at least 10 rare cancers. By 2014, TCGA expects to have amassed 5 petabytes (5 x 1015) of sequence data.3
The researchers need a total of 500 qualified cases per histopathologic diagnosis to have data with enough power to detect recurrent mutations found in just 3% to 5% of cases. However, the goal for rare tumor types is to characterize approximately 50 cases across at least 10 rare cancers. The first rare tumor type to be characterized was chromophobe kidney cancer, which had 65 cases qualified as of Fall 2012.
TCGA is currently accepting tissue samples for many tumor types; however, accrual will end around the end of 2013. Tissues must be frozen resection samples representing tumors that are primary and untreated, and the tumor samples must be paired with a source of germline DNA. TCGA welcomes additional collaborators, as tumors will need to be collected worldwide to meet the size and scope of the project. Requirements for tissue samples for TCGA can be found at http://cancergenome.nih.gov/cancersselected/biospeccriteria, and requests for more information on collaborating with the project should be sent to email@example.com.
Notably, TCGA project has already impacted how different centers collect samples for research, explained Shaw. TCGA developed a guidance document for informed consent that helps prospective clinicians gain approval from local Institutional Review Boards. The work of TCGA has established new policies and documents for genomic studies to help patients and doctors better decide if donating tissue samples to TCGA is right for them. Shaw said, “Our model has resulted in changes in practice from consent to data collection, and that alone will have a role in research for decades to come.”
When asked about the role of nurses in TCGA, Shaw said, “Research nurses are an integral part of what TCGA does at the level of the individual institutions that participate. They can help improve the overarching process—including the writing of stronger consent forms that push research forward. Nurses also can provide us with insight into the clinical data necessary and the most efficient processes to collect and assess the data points that are needed for collection.”