Cancer Genomics in the world

 

What is Cancer Genomics?

Cancer Genomics is relatively new sub-field of genomics, which applies high throughput technologies to characterize genes associated with cancer. Cancer is a genetic disease caused by accumulation of mutations to DNA leading to unrestrained cell proliferation and neoplasm formation. The goal of Cancer Genomics is to identify new oncogenes or tumor suppressor genes that may provide new insights into cancer diagnosis, predicting clinical outcome of cancers, and new targets for cancer therapies. The success of targeted cancer therapies such as Gleevec, Herceptin, and Avastin raised the hope for oncogenomics to elucidate new targets for cancer treatment [1].

Besides understanding the underlying genetic mechanisms that initiates or drives cancer progression, one of the main goals of oncogenomics is to allow for the development of personalized cancer treatment. Cancer develops due to an accumulation of mutations in DNA. These mutations accumulate randomly, and thus, different DNA mutations and mutation combinations exist between different individuals with the same type of cancer. Thus, identifying and targeting specific mutations which have occurred in an individual patient may lead to increased efficacy of cancer therapy.

The completion of the Human Genome Project has greatly facilitated the field of oncogenomics and increased abilities of researchers to find cancer causing genes. In addition, the sequencing technologies now available for sequence generation and data analysis have been applied and greatly contributed to the study of oncogenomics. With the amount of research conducted on cancer genomes and the accumulation of databases documenting the mutational changes, it has been predicted that the most important cancer-causing mutations, rearrangements, and altered expression levels will be catalogued and well characterized within the next decade. Cancer research may look either on the genomic level at DNA mutations, the epigenetic level at methylation or histone modification changes, the transcription level at altered levels of gene expression, or the protein level at altered levels of protein abundance and function in cancer cells. Cancer Genomics focuses on the genomic, epigenomic, and transcript level alterations in cancer.

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- Goals of cancer genomics -

 

Genome-based cancer research projects


Many research groups in several conturies including United States and Britain have made great efforts to find a cure for cancer by increased research to improve the understanding of cancer biology and the development of more effective cancer treatments, such as targeted drug therapies. The aim of such efforts is to eradicate cancer as a major cause of death. The signing of the National Cancer Act of 1971 by then U.S. President Richard Nixon is generally viewed as the beginning of the war on cancer, though it was not described as a "war" in the legislation itself [2].

Despite significant progress in the treatment of certain forms of cancer (such as childhood leukemia [3]), cancer in general remains a major cause of death nearly 40 years after this war on cancer began [4], leading to a perceived lack of progress[5-7] and to new legislation aimed at augmenting the original National Cancer Act of 1971 [8]. New research directions, in part based on the results of the Human Genome Project, hold promise for a better understanding of the genetic factors underlying cancer, and the development of new diagnostics, therapies, preventive measures, and early detection ability.

The rise of a new class of molecular technologies developed during the Human Genome Project opens up new ways to study cancer and holds the promise for the discovery of new aspects of cancer biology that could eventually lead to novel, more effective diagnostics and therapies for cancer patients [9-11]. These new technologies are capable of screening many biomolecules and genetic variations in a single experiment and are employed within functional genomics and personalized medicine studies. The followings are current on-going projects of cancer research in the world.


TCGA

The Cancer Genome Atlas (TCGA) is a project to catalogue genetic mutations responsible for cancer, using genome analysis techniques started in 2005 [12][13]. TCGA represents an effort in the War on Cancer that is applying recently developed high-throughput genome analysis techniques and is seeking to improve our ability to diagnose, treat, and prevent cancer through a better understanding of the molecular basis of this disease.

In 2006 the National Cancer Institute and the National Human Genome Research Institute selected people and laboratories that will participate in this project. The goal of the project was to provide systematic, comprehensive genomic characterization and sequence analysis of three types of human cancers glioblastoma multiforme, lung, and ovarian cancer.

The project is unique in terms of the size of the patient cohort interrogated (scheduled are 500 patient samples, far more than most genomics studies), and the number of different techniques used to analyze the patient samples. Techniques that are being used include gene expression profiling, copy number variation profiling, SNP genotyping, genome wide DNA methylation profiling, microRNA profiling, and exon sequencing of at least 1,200 genes. Recently the group organizing the TCGA announced that they would sequence the entire genomes of some tumors and at least 6,000 candidate genes and microRNA sequences. This targeted sequencing is actively being performed by all three sequencing centers using hybrid-capture technology. A gene list is available on the TCGA website. In phase II, TCGA will perform whole exon sequencing on 80% of the cases and whole genome sequencing on 80% of the cases used in the project.

TCGA has expanded in 2009 from a pilot to a large scale project. Over the next 5 years TCGA will provide genomic characterization and sequence analysis on 20-25 different tumor types. In 2010 a number of new centers have been funded to characterize these new tumor types. There are Genome Characterization Centers (GCCs) and Genome Data Analysis Centers (GDACs) funded to move this project into the next phase. The fact that the RFA for the expanded phase of TCGA included the specific funding of these analysis cores reflects the growing need for dedicated funding to bioinformatics in these large scale programs.

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Cancer Genome Project

The Cancer Genome Project, based at the Wellcome Trust Sanger Institute, aims to identify sequence variants/mutations critical in the development of human cancers. Like TCGA project within the United States, the Cancer Genome Project represents an effort in the War on Cancer to improve cancer diagnosis, treatment, and prevention through a better understanding of the molecular basis of this disease. The Cancer Genome Project, led by Michael Stratton and Andy Futreal, combines knowledge of the human genome sequence with high throughput mutation detection techniques.

The Cancer Genome Project holds several data resources such as the Catalogue Of Somatic Mutations In Cancer (COSMIC). COSMIC is an online database of somatically acquired mutations found in human cancer. Somatic mutations are those that occur in non-germline cells that are not inherited by children. COSMIC curates data from papers in the scientific literature and large scale experimental screens from the Cancer Genome Project at the Sanger Institute. The database is freely available without restriction via its website (http://www.sanger.ac.uk/genetics/CGP/cosmic/).

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International Cancer Genome Consortium

The International Cancer Genome Consortium (ICGC) is a voluntary scientific organization that provides a forum for collaboration among the world's leading cancer and genomic researchers. The ICGC was launched in 2008 to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of main importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

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References

  1. Strausberg, R.L., et al., Oncogenomics and the development of new cancer therapies. Nature, 2004. 429(6990): p. 469-474.
  2. "National Cancer Act of 1971". National Cancer Institute. Retrieved 2009-08-09.
  3. Kersey, John H. (1997). "Fifty Years of Studies of the Biology and Therapy of Childhood Leukemia". Blood 90 (11): 4243-4251.
  4. Kolata, Gina (April 24, 2009). "As Other Death Rates Fall, Cancer’s Scarcely Moves". The New York Times. Retrieved 2009-06-10.
  5. The War on Cancer A Progress Report for Skeptics Skeptical Inquirer, Volume 34.1, January / February 2010
  6. Hughes R. (2006). "The War on Cancer: An Anatomy of Failure, a Blueprint for the Future (book review)". JAMA 295: 2891?2892. doi:10.1001/jama.295.24.2891. ISBN 1-4020-3618-3.
  7. Sharon Begley (2008-09-15). "Rethinking the War on Cancer". Newsweek. Retrieved 2008-10-09.
  8. "Kennedy, Hutchison Introduce Bill To Overhaul 1971 National Cancer Act". Medical News Today. 2009-03-30. Retrieved 2009-03-30.
  9. NCI Director's Challenge: Toward a Molecular Classification of Cancer". NCI's Cancer Diagnosis Program. Retrieved 2008-11-05.
  10. Bernadine Healy M.D. (2008-10-23). "Breaking Cancer's Gene Code". U.S. News & World Report. Retrieved 2008-10-28.
  11. "Empowering Cancer Research". NCI's "The Nation's Investment in Cancer Research". Archived from the original on 2008-06-16. Retrieved 2008-11-05.
  12. "The Cancer Genome Atlas homepage". National Cancer Institute. Retrieved 2009-04-28.
  13. NIH Launches Cancer Genome Project. Washington Post Dec 14, 2005