Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome
High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites a...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2010
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| In: |
Familial cancer
Year: 2010, Volume: 9, Issue: 2, Pages: 173-179 |
| ISSN: | 1573-7292 |
| DOI: | 10.1007/s10689-009-9307-z |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s10689-009-9307-z
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| Author Notes: | Miriam Reuschenbach, Matthias Kloor, Monika Morak, Nicolas Wentzensen, Anja Germann, Yvette Garbe, Mirjam Tariverdian, Peter Findeisen, Michael Neumaier, Elke Holinski-Feder, Magnus von Knebel Doeberitz |
| Summary: | High level microsatellite instability (MSI-H) occurs in about 15% of colorectal cancer (CRCs), either as sporadic cancers or in the context of hereditary non-polyposis cancer or Lynch syndrome. In MSI-H CRC, mismatch repair deficiency leads to insertion/deletion mutations at coding microsatellites and thus to the translation of frameshift peptides (FSPs). FSPs are potent inductors of T cell responses in vitro and in vivo. The present study aims at the identification of FSP-specific humoral immune responses in MSI-H CRC and Lynch syndrome. Sera from patients with history of MSI-H CRC (n = 69), healthy Lynch syndrome mutation carriers (n = 31) and healthy controls (n = 52) were analyzed for antibodies against FSPs using peptide ELISA. Reactivities were measured against FSPs derived from genes frequently mutated in MSI-H CRCs, AIM2, TGFBR2, CASP5, TAF1B, ZNF294, and MARCKS. Antibody reactivity against FSPs was significantly higher in MSI-H CRC patients than in healthy controls (P = 0.036, Mann-Whitney) and highest in patients with shortest interval between tumor resection and serum sampling. Humoral immune responses in patients were most frequently directed against FSPs derived from mutated TAF1B (11.6%, 8/69) and TGFBR2 (10.1%, 7/69). Low level FSP-specific antibodies were also detected in healthy mutation carriers. Our results show that antibody responses against FSPs are detectable in MSI-H CRC patients and healthy Lynch syndrome mutation carriers. Based on the high number of defined FSP antigens, measuring FSP-specific humoral immune responses is a highly promising tool for future diagnostic application in MSI-H cancer patients. |
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| Item Description: | Online veröffentlicht: 2. Dezember 2009 Gesehen am 15.05.2023 |
| Physical Description: | Online Resource |
| ISSN: | 1573-7292 |
| DOI: | 10.1007/s10689-009-9307-z |