FPGG017 - A characterization of bladder cancer progression based on expression data obtained through exon microarrays

Research Project

Large scale analysis tools, like arrays and more recently high throughput sequencing have given a considerable new impetus in cancer research. Arrays allowing transcript analysis (in general one value per gene) have been introduced in the late 1990s and are now widely used. It is only recently that “exon” arrays, a relatively new type of microarray which enables us to get information about the splicing variants of a gene, have been developed by the Affymetrix company. As it is commonly observed relatively to those technologies, the gap between the tools to produce the data and the informatics and statistical tools to analyse them is very important. This gap has considerably slowed down the use of exon arrays. However the data obtained by this type of array will bring a new dimension in cancer research. The importance of splicing variants analysis is obvious, as splicing variants from the same gene can have very different properties. For example BCL2L1 has two splicing variants, Bcl-X(L) which is anti-apoptotic and Bcl-X(S) which is apoptotic. Likely due to the difficulty of exon array data analysis, only a few splicing events associated with tumour progression have been reported, most of them being detected by classical techniques rather than using microarray data.
Although quantification of splicing events is possible by high throughput sequencing, it is for the moment prohibitive and it is very difficult to estimate when or if the price of high throughput sequencing will be lower than the price of exon arrays. Eventually, it is likely that the two techniques will be complementary.

Starting from exon array data already available from bladder tumours representing the various stages and grades of the disease, this project aims at:
1) Identifying new subgroups of tumours
2) Identifying new markers of progression
3) Identifying new fusion transcripts
4) Identifying new candidate genes to be involved in tumour progression
5) Developing new statistical and bioinformatics tools to analyse exon array data

 

Research Teams

Molecular oncology - Institut Curie
Main Activity : Biology
François Radvanyi

Research Laboratory in silico of molecules for therapeutic goal - Paris VII
Main Activity : Bioinformatics
Frédéric Guyon

Department of Biostatistics - Curie Hospital
Main Activity : Statistics
Xavier Paoletti

Department of Anatomopathology & Department of Urology - Henri Mondor Hospital
Main Activity : Anatomopathology / Clinics
Yves Allory