人T细胞因子4外显子3～9突变在微卫星不稳定性直肠癌中的意义

Significance of mutations of exons 3-9 of human T cell transcription factor-4 in sporadic rectal cancer with microsatellite instability

目的 探讨人T细胞因子4（hTCF-4）外显子3～9突变在微卫星不稳定散发性直肠癌中的意义.方法 对102例散发性直肠癌患者进行微卫星标记遗传筛选.11例证实为高频率微卫星不稳定.对这11例以及来源于不同样本的微卫星稳定和正常组织病例各5例进行hTCF-4基因外显子3～9编码区测序分析.结果 研究揭示几个新的突变和序列变异体.在外显子4,一个为导致氨基酸由Q131T改变为S132I的一个四位连续变化（391insA、392G＞A、393A＞G and 395delC）,另一个为核苷酸缺失（395delC）,这些改变分别存在于不同的高频率微卫星不稳定病例（5/10,50%和4/10,40%）,而对照组缺乏.结论 这些突变与高频率微卫星不稳定性散发性直肠癌患者高度相关.

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.