Not only cancer genome: Part 2

At April's AACR meeting, NIH Director Francis Collins stressed the relevance of the Cancer Genome Atlas (TGCA), a project that aims to understand the genetics of cancer using innovative genome analysis technologies [1].

Following the launch of comprehensive cancer genome projects such as TGCA in the US and the Cancer Genome Project in the UK [2], genome scientists and funding agencies met in Toronto in October 2007 to discuss setting up an international consortium. As a result, the International Cancer Genome Consortium (ICGC) was launched, with the aims of coordinating a large number of research projects -such as the TGCA and the CGP – and generating comprehensive catalogues of cancer genomic abnormalities [3].

The ultimate aim of the consortium is to make data available to the entire research community as rapidly as possible, and with minimal restrictions [4,5].

But the cancer genome is not the only issue at stake, as pointed out by Manuel Esteller (Cancer Epigenetics and Biology Program, Barcelona) and Olli Kallioniemi (Translational Genome-Scale Biology Group, Turku, Finland )[6] at the EACR 21 meeting in Oslo, June 2010. While the former stressed the importance of the methylome in understanding the link between the genetics and the environment in the ethiopathogenesis of cancer, the latter talked about the importance of transcriptome in cancer and about the possibilities offered by an online tool such as GeneSapiens in identifying news indications for existing cancer drugs.

Olli Kalliomeni is the Director of the Gene Sapiens Project, a bioinformatics group that provides unique data analysis options and capabilities using an extensive in-house database of the human transcriptome [7].

This database is the world's largest fully integrated and annotated human gene expression data source, containing a multitude of annotation information for each sample, including tissue of origin, detailed cancer type and histological details. The project originally started as a way to study a single gene's co-expression, by gathering a number of experiments and studying the expression patterns of a handful of genes, but it is now developing and applying high-throughput genomics and transcriptomics analyses of cancer, bioinformatic modelling and the functional, high-throughput analysis with RNAi and drugs using cell and lysate microarrays [8-10].

According to Kallioniemi, GeneSapiens could turn out to be an excellent translational tool for drug 'repositioning' analysis, i.e. for finding new targets and uses for existing drugs. The strategy is to integrate data from the aforementioned platforms in order to identify key drug targets and explore mechanisms of drug action and resistance.

The ultimate task of the genome and epigenome cancer projects should be translation to the clinics, with the development of personalized, individualized molecular oncology. By combining several tools, such as full genome sequencing, molecular profiling, phosphoproteomics, chemical cancer biology (e.g. establishment of a cell line, drug screening, establishment of a xenograft), while putting the patient at the center of the study.

As Kallioniemi put it: "Taking molecular profiles toward the clinical diagnostic setting is the final frontier and will require standardized technologies, quality control, and prospective testing in large series of patient cohorts. This is a major effort for any single molecular profiling platform, and an enormous challenge for the clinical application of integrated multiplatform".[10]

To reach these shared goals, the different projects from both sides of the Atlantic should closely collaborate, as stressed also by AACR President Elizabeth Blackburn and EACR President Anne-Lise Børresen-Dale at the inaugural address of the conference on Saturday, June 26, 2010.

References

[1] Cancer Genome Atlas website, available at http://cancergenome.nih.gov/(accessed June 30, 2010).

[2] The UK Cancer Genome Project, website, available at http://www.sanger.ac.uk/genetics/CGP/ (accessed June 30, 2010).

[3] International Cancer Genome Consortium website, available at http://www.icgc.org/ (accessed June 30, 2010).

[4] International Cancer Genome Consortium. International network of cancer genome projects. Nature 2010;464(7291):993-8.

[5] Document stating the goals of the International Cancer Genome Consortium, pdf available at http://www.icgc.org/files/ICGC_April_29_2008.pdf(accessed June 30, 2010).

[6] Professor Olli Kallioniemi's Translational Genome-Scale Biology Group, Turku, Finland website available at http://tgsb.vtt.fi/kallioniemi%20group.htm(accessed June 30, 2010).

[7] Tuupanen S, Turunen M, Lehtonen R, et al. The common colorectal cancer predisposition SNP rs6983267 at chromosome 8q24 confers potential to enhanced Wnt signaling. Nature Genetics 2009;41:885-890.

[8] Melo SA, Ropero S, Moutinho C, et al. A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function. Nature Genetics 2009;41,365-370.

[9] Gene Sapiens project, website available at http://www.genesapiens.org/(accessed June 30, 2010).

[10] Edgren H, Kallioniemi O. Integrated breast cancer genomics. Cancer Cell 2006;10(6):453-4.