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• Development of tools for diagnostic validation of molecular<br />
signatures for cancers of high population impact,<br />
namely of the colon, breast and lung. This will enable<br />
translation into clinical use of signatures obtained<br />
through the cancer-oriented genomic screenings performed<br />
by the participating units. In particular, the<br />
project is expected to defi ne and validate prognostic<br />
signatures associated with the tendency of the abovementioned<br />
cancers to give rise to metastasis.<br />
• Establishment of a shared bioinformatic platform for<br />
functional oncogenomics data handling and standardisation.<br />
This will require a concerted eff ort towards<br />
codifi cation of the various biological assays according to<br />
specifi c functional features analysed by each assay,<br />
using for example the Gene Ontology as a template<br />
(www.geneontology.org), and the sharing of analysis software<br />
and tools. Towards the same aim, a web-accessible<br />
platform based on the Distributed Annotation System<br />
(www.biodas.org) will be implemented.<br />
Expected results<br />
The project will go through three main phases:<br />
Phase I (year 1): Initial set-up of experimental procedures for<br />
systematic cancer gene functional analysis and clinical validation;<br />
establishment of standards and tools for HTP data<br />
sharing and mining.<br />
Phase II (years 2-3): Scaled-up, high-throughput gene functional<br />
analysis and clinical diagnostic validation of new<br />
cancer molecular signatures, and identifi cation of new<br />
molecular targets for innovative cancer therapy.<br />
Phase III (year 4): Final collection of results, dissemination of<br />
technologies and deliverables to the European cancer<br />
research community and cancer hospitals. Exploitation of<br />
the achieved results, mainly as new cancer diagnosis tools<br />
and the screening of new targets for cancer drug discovery.<br />
The TRANSFOG project will deliver a consistent and integrated<br />
amount of functional data on genes of, as yet,<br />
unknown activity and biological role. In the process of reaching<br />
this objective, the participating units will be enabled to<br />
set up truly post-genomic eff orts toward systematic gene<br />
functional characterisation. New technologies will be developed<br />
that will allow exploration of gene regulatory networks,<br />
protein- protein interactions and high-throughput cell-based<br />
evaluation of basic biological functions, such as motility,<br />
growth, apoptosis, invasion, adhesion, polarisation and more<br />
158<br />
complex processes, as in vitro epithelial morphogenesis and<br />
angiogenesis. The technologies for systematic gene functional<br />
characterisation developed here will be useful for<br />
functional studies involving a variety of physiological and<br />
pathological processes, and will be made available to the<br />
scientifi c community in the frame of a collaborative research<br />
network. The bioinformatic networking endowed with the<br />
project will enable participating units to share tools for data<br />
handling, database exploration and functional gene annotation.<br />
It will also facilitate integration of the present network<br />
with other EC-funded networks and with the European and<br />
global post-genomic community.<br />
Potential applications<br />
A crucial issue in genomics is to develop enabling technologies.<br />
TRANSFOG will tackle this issue by developing:<br />
• tools and standards for genomic data sharing, which will<br />
allow the results of cancer-oriented genomic screenings<br />
carried out by the consortium to be merged or made<br />
available in databases, thus generating a prioritised list<br />
of candidate cancer genes;<br />
• plasmid collections carrying FL-cDNAs or siRNAs to achieve<br />
gainor loss-of-functions of the identifi ed candidates.<br />
Within a few years, competitive research will rely on the<br />
availability of genome-wide collections enabling systematic<br />
gene gain- or lossof- function and protein-protein interaction<br />
studies. Similarly, only high-throughput biochemical<br />
and biological assays will take full advantage of such collections,<br />
together with bioinformatic resources to handle and<br />
mine the data. A great advantage of a smaller collection<br />
focused on cancer gene discovery, like the one proposed<br />
here, is that it will enable functional analysis at a midthroughput<br />
level, with a higher probability of success in the<br />
timeframe of the project. The know-how developed in the<br />
process of generating and employing such a collection will<br />
provide the basis for competitive, larger-scale studies to be<br />
carried out later on at the European level.<br />
The willingness to understand and cure cancer will be the<br />
driving force for generating functional genomic technologies<br />
specifi cally aimed at improving management of the<br />
oncological patient. Indeed, a more precise evaluation of the<br />
tendency of a tumour to give rise to metastases will have<br />
a great social impact, particularly in helping reduce mortality<br />
and, at the same time, reducing overtreatment of patients<br />
that would not require aggressive anticancer therapy, and<br />
promoting direct, early exploration of alternative therapeutic<br />
strategies in patients with diagnostic signatures that predict<br />
poor prognosis.<br />
CANCER RESEARCH PROJECTS FUNDED UNDER THE SIXTH FRAMEWORK PROGRAMME