Linnebacher Michael, Wienck Anne, Boeck Inga, Klar Ernst
Department of General, Thoracic, Vascular and Transplant Surgery, University of Rostock, Rostock, Germany.
J Biomed Biotechnol. 2010;2010:841451. doi: 10.1155/2010/841451. Epub 2010 Mar 18.
Microsatellite instability (MSI-H) induced by defects of the DNA mismatch repair system results in insertion or deletion of single nucleotides at short repetitive DNA sequences. About 15% of sporadic and approximately 90% of hereditary nonpolyposis colorectal cancers display MSI-H. When affecting coding regions, MSI-H results in frameshift mutations and expression of corresponding frameshift peptides (FSPs). Functional tumor promoting relevance has been demonstrated for a growing number of genes frequently hit by MSI-H. Contrary, immune reactions against FSPs are involved in the immune surveillance of MSI-H cancers. Here, we provide conclusive data that the (-1) frame of U79260(FTO) encodes an HLA-A0201-restricted cytotoxic T cell epitope (FSP11; TLSPGWSAV). T cells specific for FSP11 efficiently recognized HLA-A0201((pos)) tumor cells harboring the mutated reading frame. Considering the exceptionally high mutation rate of U79260(FTO) in MSI-H colorectal carcinoma (81.8%), this recommends that FSP11 be a component of future vaccines.
DNA错配修复系统缺陷引起的微卫星不稳定性（MSI-H）导致短重复DNA序列处单核苷酸的插入或缺失。约15%的散发性结直肠癌和大约90%的遗传性非息肉病性结直肠癌表现为MSI-H。当影响编码区域时，MSI-H会导致移码突变和相应移码肽（FSPs）的表达。越来越多经常受MSI-H影响的基因已被证明具有促进肿瘤功能的相关性。相反，针对FSPs的免疫反应参与了MSI-H癌症的免疫监视。在此，我们提供确凿数据表明，U79260（FTO）的（-1）读框编码一种HLA-A0201限制性细胞毒性T细胞表位（FSP11；TLSPGWSAV）。对FSP11特异的T细胞能有效识别携带突变读框的HLA-A0201（阳性）肿瘤细胞。鉴于MSI-H结直肠癌中U79260（FTO）的突变率异常高（81.8%），这表明FSP11应成为未来疫苗的一个组成部分。
