Genome-wide expression profile of sporadic gastric cancers with microsatellite instability

• DOI: 10.1016/j.ejca.2008.10.032
• Publication Date: 2008-12-09T15:14:57Z
• Authors: Mariarosaria D’Er...; Emanuele de Rinaldis; Monica F. Blasi; Valentina Viti; Mario Falchetti; Angelo Calcagnile; Francesco Sera; Calogero Saieva; Laura Ottini; Domenico Palli; Fabio Palombo; Alessandro Giuliani; Eugenia Dogliotti
• Keywords: p53; Male; 610; Down-Regulation; DNA Mismatch Repair; Promoter Regions; 03 medical and health sciences; Genetic; Stomach Neoplasms; 80 and over; Humans; dna repair; gastric cancer; gene expression; microsatellite instability; gastric cancers, microsatellite instability; Promoter Regions, Genetic; Aged; Oligonucleotide Array Sequence Analysis; Aged, 80 and over; Neoplastic; 0303 health sciences; Gene Expression Profiling; Middle Aged; Genes, p53; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; Phenotype; Gene Expression Regulation; Genes; Female; Microsatellite Instability

Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed. Unsupervised analysis showed that the immune and apoptotic gene networks efficiently discriminated these two cancer types. Hierarchical clustering analysis revealed numerous gene expression changes associated with the MSI phenotype. Amongst these, the p53-responsive genes maspin and 14-3-3 sigma were significantly more expressed in tumours with than without MSI. A tight immunosurveillance coupled with a functional p53 gene response is consistent with the better prognosis of MSI cancers. Frequent silencing of MLH1 and downregulation of MMR target genes, such as MRE11 and MBD4, characterised MSI tumours. The downregulation of SMUG1 was also a typical feature of these tumours. The DNA repair gene expression profile of gastric cancer with MSI is of relevance for therapy response.