A89

Background: MicroRNAs (mirs) are short non-coding RNAs that regulate gene expression through post-transcriptional suppression of mRNA.. Rosetta Genomics has developed an integrative bioinformatics/biological approach which led to the discovery and validation of several hundreds of novel human mirs.Objectives: Apply this large platform of miRNAs, to cancer diagnostics and treatment evaluation, including both early detection, disease stratification and response to treatment,in a number of major human solid tumors.Materials and Methods: Improved methods for extraction of mirs from fresh , frozen ,and paraffin embedded tissues, as well as from body fluids. In house development of highly sensitive mir expression profiling by mir microarrays, Luminex and Real Time PCR.. Tissue samples drawn mostly from paraffin embedded tissues with sufficient clinical data on each specimen analyzed.Results: Several hundreds of tissue samples- paired and unpaired tumor and normal tissues, from Breast, Colon, Lung, Liver, Bladder and Prostate have been studied. A clear and reproducible differential mir expression profile is associated with each cancer. For every cancer studied there are mirs that are highly upregulated and mirs that are down regulated in the tumors in comparison to the normal tissues. In each tumor, the number of mirs differentially expressed is limited and thus cancer signatures are smaller than in regular gene/cancer signatures reported . Tissue specificity of mirs enables the distinction and diagnosis of tissue origin of the tumors. Correlation of the mir expression profile to stage, prognosis and response to treatment is being analyzed.Conclusions; 1) MicroRNA expression profile is a very useful diagnostic tool in solid tumors. 2) Specific cancer associated mir signature seems to be smaller in size and is tissue specific. 3) Specific cancer associated mir expression profile may serve as a basis and target for future cancer therapeutics.

[First AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development, Sep 12-15, 2006]