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Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 841451, 6 pages
http://dx.doi.org/10.1155/2010/841451
Research Article

Identification of an MSI-H Tumor-Specific Cytotoxic T Cell Epitope Generated by the ( 1) Frame of U79260(FTO)

Section of Molecular Oncology and Immunotherapy, Department of General, Thoracic, Vascular and Transplant Surgery, University of Rostock, Schillingallee 35, 18057 Rostock, Germany

Received 17 November 2009; Accepted 14 January 2010

Academic Editor: Zhengguo Xiao

Copyright © 2010 Michael Linnebacher et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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 ( ) frame of U79260(FTO) encodes an HLA-A0201-restricted cytotoxic T cell epitope (FSP11; TLSPGWSAV). T cells specific for FSP11 efficiently recognized HLA- 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.