Significance of mutations of exons 3-9 0f human T cell transcription factor4 in sporadic rectal cancer with microsatellite instability

Objective To establish the role of human T cell transcription factor-4 (hTCF-4) mutation status associated with sporadic rectal cancer with microsatellite instability (MSI). Methods Geno-typing using microsatellite markers was studied in the 102 sporadic rectal cancer patients and then sequence analysis of the coding region of the exons 3-9 of hTCF-4 gene was carried out in a group of cases with high-frequency MSI (MSI-H) (n = 11) and controls (n - 10). Results This study revealed several novel mutations and sequence variants. In exon 4 one local combined alteration (391insA, 392G > A, 393A > G and 395delC) and another nonsense mutation (395delC) , being presence in most of MSI-H cases (5/10, 50% and4/10, 40% , respectively), but completely absence in the controls, were likely to have any functional relevance. Conclusion The mutations and sequence variants in exon 4 may be involved in a portion of patients with sporadic rectal cancers characterized by MSI-H. Key words: Carcinoma of rectum;  T cell transcription factor-4;  Mutation