| Summary: | <p>Abstract</p> <p>Background</p> <p><it>SnoN </it>is an important regulator of the transforming growth factor beta (TGFβ) signalling pathway and has been shown to exhibit both tumour promotion and suppression activity.</p> <p>Methods</p> <p>To further explore the role of this complex molecule in colorectal tumorigenesis, we examined 52 paired normal and tumour colorectal specimens stratified by level of microsatellite instability; 18 with high-level microsatellite instability (MSI-H) and 34 microsatellite stable (MSS). <it>SnoN </it>transcript expression was quantitated by real-time PCR and analysed with respect to clinical indicators of prognosis.</p> <p>Results</p> <p>Within the MSI-H subgroup, <it>SnoN </it>was commonly either up-regulated (6/18, 33%) or down-regulated (7/18, 39%). A significantly different distribution of <it>SnoN </it>expression was observed in MSS cancers compared with MSI-H (P ≤ 0.001). Whilst 17/34 (50%) of MSS tumours demonstrated up-regulation, none showed down-regulated expression. Within the MSI-H subgroup, up-regulation was significantly correlated with lack of repeat tract mutation in the <it>TGFβRII </it>gene (P ≤ 0.025), suggesting that <it>SnoN </it>is more frequently up-regulated in the presence of functional TGFβ signalling.</p> <p>Conclusion</p> <p>Together these data support the notion that SnoN has both oncogenic and tumour suppressive properties depending on other genetic changes within the tumour, and that the MSI-H pathway of colorectal tumorigenesis presents an excellent model for the study of these opposing functions.</p>
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