The cumulative risk of cancer in Fanconi anaemia (FA) patients at the age of 50 is about 80% due to the tumour suppressor role of the FA/BRCA pathway. This pathway is known to be involved in a number of sporadic cancers in the general population. Considering the molecular defect of these tumours, they are expected to be hypersensitive to the cytotoxic effects of DNA-cross-linking-based chemotherapy. the aims of this project is to get new insights into the role of the FA/BRCA pathway in genome stability and DNA damage response, to investigate the regulation of FA genes, and to interfere the FA/BRCA pathway with by use of RNA interference approaches and inhibitors to assess whether such disruption is able to chemosensitize tumour cell lines to chemotherapy. We will finally use proteomic (DIGE-MS) genomic (microarray-CGH) and protein association (ChIP) to find novel components of the FA/BRCA pathway and, therefore, to identify new tumour suppressor genes. This gene discovery approach will be applied to a collection of anonymous FA cells lines where we already disregarded all known FA
|Effective start/end date||26/07/05 → 25/07/08|
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