ARRA IMPACT REPORT:
The Cancer Genome Atlas (TCGA) Project
Public Health Burden
Cancer is the second leading cause of death in the United States after heart disease. In 2012, it is estimated that nearly 1.6 million new cases of invasive cancer will be diagnosed in this country, and more than 577,000 Americans will die of cancer.
The Cancer Genome Atlas (TCGA) is a large-scale collaborative effort co-funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), whose goal is to characterize all relevant genomic alterations in a variety of human cancers. To reach this goal, TCGA is developing and applying innovative genome sequencing and characterization technologies. Tumor samples used for TCGA must meet stringent criteria to ensure the highest quality data are produced. The requirements set by TCGA also stipulate the number of tumor samples that must be characterized to produce a comprehensive genomic profile for each cancer type. The TCGA Research Network includes a broad cross-section of the cancer research community, including basic and clinical researchers, bioinformatics specialists, bioethicists, doctors, and nurses. TCGA is a public resource, and all analytic tools and genomic data generated are freely accessible to the cancer research community.
How ARRA Funding is Supporting TCGA to Accelerate Cancer Research
ARRA funding was crucial to the expansion of TCGA to include additional cancer types and tumor samples. The program expanded from two to more than 20 tissue types; ten times the number of tumor types than would have been possible without ARRA funding. The expansion allowed inclusion of common cancer types, such as lung, prostate, breast, and colorectal cancers to the TCGA tissue collection. Inclusion of a variety of tumor types has greatly enhanced the diversity of the TCGA genomic database and provides resources needed by investigators pursuing varied fields of cancer research. The influx of ARRA funds also supported an increase in the TCGA sequencing capacity. The robust capacity will ensure timely processing of the new tissue samples and submission of new genomic information to the database (https://tcga-data.nci.nih.gov/tcga/tcgaHome2.jsp).
Cancer is a disease of the genome, and each cancer has its own set of genomic changes. TCGA is supporting research by providing the genomic characterization of many cancer types to the cancer research community. The genomic information provided through TCGA is a critical resource that is helping researchers uncover the molecular mechanisms of cancer, identify molecularly distinct subtypes of broader cancer types, and discover more effective treatments for each cancer subtype. With a large variety of tumor genomic data available, which was greatly expanded with ARRA funding, researchers will be able to better understand the genomic changes that are unique to certain cancer types that could lead to identification of potential targets for drug development.
ARRA funding accelerated the scientific progress of TCGA, including collection of additional cancer types, comparative studies among tissue types, and supporting the development of analytical tools. TCGA researchers are currently preparing manuscripts for publication of the genomic characterization of breast, colorectal, lung, kidney, and endometrial cancers, all tissue types that were collected under the expansion of TCGA supported by ARRA funding. Hundreds of other scientific publications have used TCGA data to support various areas of cancer research. One study of lung adenocarcinoma, a common type of non-small cell lung cancer, identified a unique molecular subclass of lung cancers that have distinct clinical traits. Another study examined the expression of certain proteins to help explain why some women with breast cancer develop resistance to certain treatments. A different study of breast cancer used TCGA data to develop molecular assays that may aid in predicting the clinical outcome of women with breast cancer.
TCGA data are also providing insights into the underlying pathways and networks that are involved in cancer. A recent publication presented a comparative analysis of the genomic changes present in a specific family of genes in glioblastoma multiforme, prostate, sarcoma, and ovarian cancers; glioblastoma multiforme and ovarian tissue were collected in the pilot phase of TCGA prior to ARRA funding, but ARRA funding accelerated the collection of the prostate and sarcoma tissue types and subsequent analyses. The genetic changes and expression patterns of these genes varied among the different types of cancer and were found to have value as prognostic indicators.
The need to analyze the large datasets generated by TCGA is also providing a much-needed boost to the development of new analytic tools to perform increasingly complicated analysis of integrated genomic information, which has also been partially supported by ARRA funding. Other approaches are developing novel ways to visualize genomic data to better draw relationships between disparate datasets.
ARRA funding supported the expansion of TCGA to include additional cancer types and fueled scientific progress in cancer genomics, including:
- 22 new cancer tumor types were added to the TCGA collection, exceeding the initial ARRA goal of adding 20 new cancer tumor types. Recently, TCGA also added 10 new rare tumor types, which will be characterized in the same way as other TCGA tumor types but across fewer samples.
Tissue samples from more than 4,000 people with cancer have been submitted for genomic sequencing, surpassing the initial ARRA goal of 3,000.
Multiple pilot projects are underway, judiciously leveraging TCGA resources to examine the following: genomics of recurrent disease; impact of systemic chemotherapy on the germline; and ultra-deep sequencing of highly heterogeneous tumors (e.g., pancreatic cancer), among other topics.
- Disease working groups composed of oncologists, pathologists, surgeons and other investigators have been formed for each of the active tumor projects to ensure the projects are designed around standard of care recommendations and cutting-edge biology.
- TCGA continues to be an active participant and promoter of the International Cancer Genome Consortium (ICGC). TCGA data currently constitute the bulk of data available through the ICGC data portal.
Contributing NIH Institutes & Centers
- National Cancer Institute (NCI)
- National Human Genome Research Institute (NHGRI)