JLE

Bulletin du Cancer

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RNA and cancer Volume 95, issue 1, janvier 2008

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Institut de génétique moléculaire de Montpellier (UMR 5535, IFR 122), 1919, route de Mende, 34293 Montpellier Cedex 5

The aim of this review is to draw the attention to the numerous steps of gene expression which operate at the RNA level and which are significant drivers of the transformation process. The analysis of genomic abnormalities was at first limited to gross chromosomal alterations and to DNA point mutations. Then came the era of transciptomes which were originally believed, since they were mRNAs, to be a faithful reflection of the expressed proteins. As a matter of fact, this first-generation transcriptomics gave only a global, quantitative, assessment of gene expression at a given locus but overlooked the qualitative diversity of the messenger population generated by alternative splicing. We will show that beyond their essential role in the regulation of functions specific to metazoan like development, alternative splicing brings about an important vulnerability to mutations which is at the origin of many pathologies including cancer. The second aspect covered by this review is that of a rather novel category of RNAs, the microRNAs which, although non-coding, functionally behave as oncogenes or tumor suppressors through the negative control they exert on conventional oncogenes or suppressors. Beyond their diagnostic and pronostic interest, these two mechanisms offer entirely novel potential therapeutic targets.