Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome

• Verfasst von: Reuschenbach, Miriam [VerfasserIn]
• Verfasst von: Kloor, Matthias [VerfasserIn]
• Verfasst von: Morak, Monika [VerfasserIn]
• Verfasst von: Wentzensen, Nicolas [VerfasserIn]
• Verfasst von: Germann, Anja [VerfasserIn]
• Verfasst von: Garbe, Yvette [VerfasserIn]
• Verfasst von: Tariverdian, Mirjam [VerfasserIn]
• Verfasst von: Findeisen, Peter [VerfasserIn]
• Verfasst von: Neumaier, Michael [VerfasserIn]
• Verfasst von: Holinski-Feder, Elke [VerfasserIn]
• Verfasst von: Knebel Doeberitz, Magnus von [VerfasserIn]
• Titel: Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome
• Verf.angabe: 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
• Jahr: 2010
• Umfang: 7 S.
• Fussnoten: Online veröffentlicht: 2. Dezember 2009 ; Gesehen am 15.05.2023
• Titel Quelle: Enthalten in: Familial cancer
• Ort Quelle: Dordrecht [u.a.] : Springer Science + Business Media B.V, 2000
• Jahr Quelle: 2010
• Band/Heft Quelle: 9(2010), 2, Seite 173-179
• ISSN Quelle: 1573-7292
• DOI: doi:10.1007/s10689-009-9307-z
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Antibodies
• Sach-SW: Frameshift peptides
• Sach-SW: Immune responses
• Sach-SW: Lynch syndrome
• Sach-SW: Microsatellite instability
• K10plus-PPN: 1845387376

Abstract

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.