Abstract
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.
Keywords
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Article info
Publication history
Published online: December 10, 2008
Accepted:
October 17,
2008
Received:
September 30,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
