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The five key objectives of the TRANSFOG project are:
- (I.) Identification of novel cancer-related genes of high clinical-diagnostic potential,
with a specific focus on progression and metastasis of colon, breast, lung cancer.
This will be achieved mainly through extensive gene expression profiling of tumour/metastasis
samples and of cell-based models of cancer progression. To extend the exploration
range, differential proteomics and epigenetic analysis are also planned. The foreseen
outcome is a ranked list of novel candidate cancer genes emerging from integration
of the screening results, that will undergo functional characterization and/or diagnostic
validation.
- (II.) Set-up of technologies for systematic cancer gene functional analysis and
for identification of new molecular targets. Gene functional analysis will be enabled
by assembling collections of full-length cDNAs and of short interfering RNAs (siRNAs)
subcloned in expression plasmids, to assess the consequences of gene gain- or loss-of-function
in cell-based and preclinical models.
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(III.) Systematic exploration of oncogenic/antioncogenic signalling pathways, epigenetic
regulatory mechanisms. Taking advantage of the FL-cDNA and siRNA collections made
available by the project, cell-based experimental systems to study protein-protein
interaction, reporter gene expression and epigenetic modifications will be exploited
for systematic analysis of the candidate genes. This will result in datasets of
protein-protein interaction, transcriptional and epigenetic regulation allowing
a comprehensive overview of the alterations in signalling and regulatory networks
involved in cancer progression.
- (IV.) Development of tools for diagnostic validation of molecular signatures for
cancers of high population impact, namely: colon, breast and lung. This will enable
translation into clinical use of signatures obtained through the cancer-oriented
genomic screenings performed by the participating Units. In particular, the project
is expected to define and validate prognostic signatures associated with the tendency
of the above mentioned cancers to give rise to metastasis.
- (V.) Establishment of a shared bioinformatic platform for functional oncogenomics
data handling and standardization. This will require a concerted effort towards
codification of the various biological assays according to specific functional features
analyzed by each assay, using for example the Gene Ontology as a template (
http://www.geneontology.org/
),
and the sharing of analysis software and tools. Towards the same aim, a web-accessible
platform based on the Distributed Annotation System (
http://www.biodas.org/
)
will be implemented.
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