Coordinator: Didier Auboeuf, Centre de Recherche en Cancérologie Lyon (CRCL).
Gene by gene and genome-wide analyses of alternative splicing demonstrated that alternative splicing is contributing to tumor initiation and progression. There are also many examples of druggable genes whose splicing is playing a role in therapy resistance. Analysis of molecular alterations at the exon level will allow to identify new genetic programs and consequently pathways participating to tumor progression and treatment resistance.
The main objectives of this project were to: (1) create a database storing all the available functional annotations corresponding to structural, functional, interaction, and sub-cellular localisation protein domains coded by each human exon; (2) develop a pipeline for the combinatorial, statistical and visual analysis of exon expression data in the context of networks and pathways; (3) perform a functional characterisation of the transcriptome at the exon level in a model of tumor progression; (4) focus on druggable genes to set up a strategy based on alternative splicing analysis allowing to predict the likelihood of cell resistance to targeted therapies.