Genome-wide expression profile of sporadic gastric cancers with 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.
D'Errico
Mariarosaria
M
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
de Rinaldis
Emanuele
E
Blasi
Monica F
MF
Viti
Valentina
V
Falchetti
Mario
M
Calcagnile
Angelo
A
Sera
Francesco
F
Saieva
Calogero
C
Ottini
Laura
L
Palli
Domenico
D
Palombo
Fabio
F
Giuliani
Alessandro
A
Dogliotti
Eugenia
E
D000368:Aged; D000369:Aged, 80 and over; D053843:DNA Mismatch Repair / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics*