摘要：The Cancer Genome Atlas—formerly the Human Cancer Genome Project—provides an opportunity for considering how social concerns about resource allocation are interrelated with practical decisions about specific research strategies—part of a continuing convergence between scientific and public evaluations of priorities for biomedical research funding. For example, the manner, order, and extent that The Cancer Genome Atlas selects tumor types and populations to be sampled will determine who benefits most from its findings. Those choices will be determined on the basis of both scientific and social values. By soliciting public involvement and conducting rigorous policy analysis in the design of large scientific projects such as The Cancer Genome Atlas, cancer researchers can help democratize the allocation of scientific resources and foster public confidence in biomedical research. LARGE-SCALE GENOMIC research is in the process of moving from basic science projects that provide common resources for many types of genetic research—such as the Human Genome Project, the Haplotype Map Project, and the SNP (from “single-nucleotide polymorphism”) Consortium—to disease-specific projects further down the translational path. Critiques of large investments in those basic scientific resources have focused on the relative value of genomic research compared with alternative nongenetic strategies for allocating public funds for biomedical research. 1 , 2 The emerging translational focus will raise additional questions about the relative values of focusing genomic investigations on particular diseases, phenotypes, and populations. Those latter questions are especially relevant for initiatives that coordinate significant financial resources across multiple research centers to systematically investigate disease-specific domains, and they are likely to have considerable influence in setting downstream research and clinical agendas. One such initiative is The Cancer Genome Atlas (TCGA), formerly known as the Human Cancer Genome Project. The Human Cancer Genome Project was proposed by the National Cancer Institute (NCI) and the National Human Genome Research Institute as a $1.5 billion, 10-year project. 3 The goal of TCGA is to identify genomic alterations associated with common cancer types. 4 To accomplish this goal, the initial plan of the NCI working group that came up with the idea for the Human Cancer Genome Project was to characterize 250 samples of the 50 most common tumor types for regions of genomic loss or amplification, chromosomal rearrangements, regions of aberrant methylation, and mutations in the coding regions of all human genes. Both somatic (induced) and germline (inherited) alterations in specific genes will be examined with a variety of information, including sequence data, gene expression data, and copy number and gene loss assays. 5 The aim is to provide a comprehensive frame of reference for examining molecular processes associated with carcinogenesis, which could have significant benefits for the identification of new drug targets and the use of existing pharmacological agents. A 3-year, $100 million pilot project cofunded by the NCI and the National Human Genome Research Institute to test the feasibility and utility of a larger TCGA was announced in December 2005; initial requests for applications for work on the project were issued in June 2006. 6 Although it was proposed as a US-only project, TCGA—like its basic science predecessors—has ready potential for expanding into an international collaborative. For example, a smaller-scale cancer genome project has been pursued in Great Britain by the Wellcome Trust Sanger Institute since 2000, but it has not sequenced the whole genomes of tumor cells and has instead focused on selected genes. 7 Collaboration discussions have occurred between leaders of the Sanger and National Institutes of Health projects. 5 Even without international collaboration, TCGA design choices will have consequences for how scientists study cancer worldwide and how benefits are distributed both inside and outside the United States. second-generation genomic initiatives to be subjected to considerable scrutiny by both the scientific community and the public. A full version of TCGA may never be implemented, of course, and it may have to be scaled down in size or scope. Nonetheless, by examining its potential implications for the distribution of benefits, we can gain insight into the ethical choices and policy debates that lie ahead as genomic research enters a new phase in its development.
