PerspectivesAre you interested in submitting a Perspective Article? Be sure to read The Science Advisory Board's Editorial Guides for Perspective Articles. Click here. The World Atlas of Cancer by Wim D'Haeze, Ph.D. Cancer: we all know a family member, close friend, or relative who has faced this devastating disease. Indeed, it has been estimated that in the U.S. alone, every minute, one individual dies due to cancer. Among the most common tumors are glioblastomas of the brain, lung cancer, and ovarian cancer that account for over 210,000 new cases in the U.S. every year and for an estimated 191,000 deaths in the U.S. in 2006. For decades, entire institutions have been dedicated to the understanding of tumor development research, which was recently fueled by the availability of the complete human genome sequence. Nevertheless, a pill against, for example, ovarian cancer, is not yet available on the market. Less than three years after the completion of the human genome sequence, the National Cancer Institute and the National Human Genome Research Institute, both belonging to the National Institutes of Health, have launched the $100 million TCGA (The Cancer Genome Atlas), an initiative to map and characterize the genomic changes involved in tumor growth and development. The pilot study will be performed on brain, lung, and ovarian cancer, because those three cancers account every year for a tremendous number of new cases within the U.S. and because of the availability of substantial biospecimen collections. It has been proposed that intracellular genetic changes lie at the heart of all forms of cancer. The identification of oncogenes – genes that are involved in cancer promotion – suggests that cancer is primarily due to de novo mutations in specific genes. The damage can be caused by the exposure to environmental factors such as radiation or UV light, or by faulty DNA repair processes. Those mutations lead to altered biological pathways that may result in uncontrolled cell replication, growth, or regeneration, and as a consequence, to tumor formation. Now that the three billion DNA base pairs of the human genome have been mapped, it is necessary to evaluate (i.e., sequence) the genome of cancerous cells and compare those with corresponding genome sequences of normal cells to identify the major genetic changes that drive tumor development. The Brigham and Women’s Hospital (Boston, Massachusetts), the MD Anderson Cancer Center (Houston, Texas), and the Children’s Hospital (Columbus, Ohio) partner together in The Cancer Genome Atlas pilot initiative to facilitate the delivery of lung, brain, and ovarian cancer tissue samples. The overall objective of The Cancer Genome Atlas initiative is to identify and map genetic changes that cause normal cells to develop into cancerous cells. This will allow us to pinpoint the molecular basis of various cancers by combining the knowledge obtained from analyzing the entire human genome sequence and its comparison with genome sequences of cancerous cells. The NIH defined the funding success factors to include completion of genomic analysis of the three cancer types that were initially chosen and the differentiation of cancer subtypes based on genomic alterations in genes associated with cancer. Importantly, the databases that will arise from The Cancer Genome Atlas initiative will be publicly available to all scientists and individuals who are interested in this information. The atlas of information generated will enable scientists worldwide to engineer and develop new diagnostic tools for the early detection of tumor development, and to produce new therapeutic strategies that will allow intervention at various stages of cancer development.  Figure 1. The Variety of defects underlying human cancer. While the future looks bright, there is still a long way to go. Independent starter studies that sequenced over ten thousand genes derived from colorectal and breast cancer tissues and compared those with the sequence of the same genes derived from neighboring healthy cells, illustrated that hundreds of genes appear to be mutated in the cancerous tissue samples. Such observations look promising, as the majority of those genes were not yet reported as being possibly mutated in cancerous tissues. However, tumor initiation and development are among the most complex processes that can occur in a human body and some thought quickly raises many important and currently unsolved questions. Identifying and mapping mutations in cancerous tissues are only the beginning, as some or maybe most, of those mutations may not have any influence on the development of the tumor (i.e., meaningless mutations). DNA has the ability to mutate, and the chance for mutation exponentially increases when cells become cancerous. Therefore, identifying a mutation in a cancer cell is not enough; it is pivotal to demonstrate that this mutation indeed plays a role in tumor development. The latter involves in-depth and, in my opinion, still time-consuming studies. Furthermore, it might be interesting and helpful to map mutations in a tumor. However, it is important to tackle the problem at its roots, and in this respect, one needs to identify those initial genetic changes and factors that occurred and lead to the development of a tumor. In addition, the factors that lead to tumor development may differ among different individuals, as is the case for the pattern of mutations. It is likely that totally different pathways may lead to the same type of cancer, and it has also been demonstrated that a tumor is not necessarily a homogenous group of cells. Consequently, the teams involved in The Cancer Genome Atlas will have to engineer robust methodologies to separate the signal from the noise. As always, strong opponents of The Cancer Genome Atlas have formulated their critiques and at a certain level, they appear to be right. Stating that the funds dedicated to The Cancer Genome Atlas are totally wasted is overkill, as the National Institutes of Health have grouped the top teams of the top U.S. institutions to do the job and an overlooking organ will be in place to ensure that the job will be well done and the money well spent. The strongest offenders of The Cancer Genome Atlas state that, “the atlas’ very premise may be fatally flawed as the system may miss the crucial mutations entirely because it is not the visible tumor tissues that are researched with The Cancer Genome Atlas initiative but the early events that turn a healthy cell into a metastatic cell that has the capacity to spread allover ones body at the very early stage of tumor development”. While this is correct, one should also realize that it is tremendously more difficult to characterize and map the initial stages of tumor development as opposed to characterizing the mutation landscape in tumor tissues that are relatively easy to harvest. In addition, it has been demonstrated that metastatic cells are also present in tumor tissues, which implies that the features characteristic for such metastatic cells will indeed be included in the global genetic spectrum of cancerous cells being analyzed as part of The Cancer Genome Atlas initiative. Thus, as outlined above, the major challenge of the initiative might be to identify this particular and crucial information among a majority of noise-type data that is less important. In summary, The Cancer Genome Atlas initiative that groups and employs the knowledge, expertise, and facilities of top researchers is a prestigious undertaking that aims to map the molecular genetic landscape of three major tumor types that cause several hundred thousand American deaths year after year. Although these large-scale analyses need time to be completed and to be fruitful, I am convinced that the outcome will add to our knowledge of tumor initiation and development and will facilitate the design of novel and effective therapies to prevent and treat cancer. Wim D’Haeze is a Bio-Engineer in Chemistry and received his Ph.D. in Biotechnology at Ghent University (Belgium) in June 2001. His doctoral thesis work was focused on the understanding of several early steps of the symbiotic interaction between the Gram-negative soil bacterium Azorhizobium caulinodans and the tropical legume Sesbania rostrata. The initial steps require the production of bacterial compounds including signal molecules and complex surface polysaccharides that are pivotal for invasion of the plant tissue and the formation of new organ tissues. In the three subsequent years, he performed post-doctoral research at the Complex Carbohydrate Research Center at the University of Georgia (Athens, GA) dealing in part with the structural and functional characterization of azorhizobial extracellular polysaccharides. Currently, Wim D’Haeze is employed as Science Writer and focuses on a new horizon regarding the molecular basis of devastative neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, in order to screen for and develop new therapeutics. In addition, he is also a freelance Medical Editor. E-mail: wim.dhaeze@sbcglobal.net ### << Previous Next >> [ View All Perspectives ] |
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