Human Heredity 11th Edition by Michael Cummings

Exercise 25

The Cancer Genome Atlas (TCGA)
Based on the initial successes of cancer genome sequencing, The National Cancer Institute and the National Human Genome Research Institute began a pilot project in 2005 called The Cancer Genome Atlas (TCGA). The project uses genomic technology-especially large-scale genome sequencing of cancer cells-to catalog the genomic changes in cancer cells. The long-term goal is to provide the tools and information needed to improve the diagnosis, treatment, and prevention of cancer.
The project has several components. First, people with selected cancers are asked to donate a small part of tumor tissue as well as normal tissue. This material will become part of a bank of material that researchers can use for genomic analysis. Because the same cancer has different genomic alterations in different patients and cells within the tumors have variations in genomic changes, it will be necessary to analyze tissue from many different samples of each type of cancer to uncover the basic changes common to all cases. Genomic changes regarded as the most significant are investigated by cancer genome sequencing centers. Information from these studies is entered into a central public database: the TCGA Data Portal.
Initially, the project focused on three types of cancer: a type of brain cancer called glioblastoma, one form of lung cancer (squamous carcinoma), and ovarian cancer. These cancers were selected for several reasons:
? Tissue samples for these cancers that meet the project's scientific and ethical standards are already available in biorepositories.
? These cancers have a poor prognosis, and information gained may have immediate use in treatment.
? Together, these cancers account for more than 250,000 new cases per year.
To date, the Cancer Genome Characterization Centers have identified thousands of genes and types of RNA for sequencing. This is not a comprehensive list, but it does represent genes and RNA types that clearly have the potential for being associated with the development of cancer. From this list, genes and RNA types for each of the three types of cancer were selected and sequenced. Data analysis compares the sequence of selected genes in cancer cells and normal cells from the same individual, giving the results a resolution of one nucleotide. For example, 600 genes identified in glioblastoma were selected for sequencing in the first round. From the results in the first round of sequencing and input from experts in this form of cancer, an additional 700 genes were selected for sequencing.
This project identified three previously unrecognized mutations in glioblastoma that occur with significant frequency in this cancer and discovered several disrupted cellular pathways. Perhaps most significant is the unearthing of a mechanism for the development of resistance to one of the drugs used to treat this form of cancer. It is hoped that this information can be used to develop a new generation of drugs for effective treatment of glioblastoma.
Work on lung cancer and ovarian cancer uncovered previously unknown mutations and networks of cellular disruptions that researchers are studying to use as starting points for new, targeted therapies. The project has expanded and is now studying more than 20 different types of cancer, including other types of brain cancer, breast cancer, and cancers of the urinary system. The list will continue to expand as more tissue samples become available.
If you had cancer, would you donate tissue samples to this project? Would you want to know about privacy issues and the possible release of parts of your medical records?