The Identification and Characterisation of LRIG Gene Family and Its Expression in Astrocytic Tumours

.................................................................................................................................. 6 LIST OF PAPERS ........................................................................................................................ 7 ABBREVIATIONS....................................................................................................................... 8 INTRODUCTION......................................................................................................................... 9 Glioma....................................................................................................................................9 Aetiology..............................................................................................................................9 Classification, grading system and its limitation ...............................................................10 Primary and secondary glioblastoma .................................................................................11 Treatment ...........................................................................................................................13 Prognosis............................................................................................................................13 Molecular Biology ............................................................................................................13 Biomarkers of interest for human glioma ..........................................................................14 Growth suppressors inactivated in human glioma.............................................................15 Growth factors activated in human glioma........................................................................17 Negative regulation of EGFR ............................................................................................21 Leucine-rich repeat superfamily....................................................................................24 LRR containing proteins in glioma and other tumours......................................................25 RATIONALE FOR THE PRESENT THESIS......................................................................... 28 SPECIFIC AIMS OF THE PRESENT STUDY ...................................................................... 29 MATERIAL AND METHODS ................................................................................................. 30 RNA samples (I, II, III, IV, V, VI) ...............................................................................30 Cell lines (III, VI)..............................................................................................................30 Clinical material (VI) .......................................................................................................31 Quantitative RT-PCR, primers, and probes (I, II, III, IV, V, VI) .........................31 Bioinformatic analysis (II, IV, V).................................................................................32 Confocal fluorescence laser microscopy (IV, VI) ....................................................32 FISH analysis (II, IV).......................................................................................................33 Northern blotting (II, IV, V)...........................................................................................33 Antibodies (III, VI)...........................................................................................................33 Immunohistochemistry (VI) ...........................................................................................34 Statistical analysis (VI)....................................................................................................34 Ethical considerations ......................................................................................................35 RESULTS AND DISCUSSION ................................................................................................. 36 CONCLUSIONS ......................................................................................................................... 46 ACKNOWLEDGEMENTS ....................................................................................................... 47 REFERENCES............................................................................................................................ 49