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

Content Provider	Springer Nature Link
Author	Reuschenbach, Miriam Kloor, Matthias Morak, Monika Wentzensen, Nicolas Germann, Anja Garbe, Yvette Tariverdian, Mirjam Findeisen, Peter Neumaier, Michael Holinski Feder, Elke Knebel Doeberitz, Magnus
Copyright Year	2009
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.
Starting Page	173
Ending Page	179
Page Count	7
File Format	PDF
ISSN	13899600
Journal	Familial Cancer
Volume Number	9
Issue Number	2
e-ISSN	15737292
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-12-02
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Antibodies Frameshift peptides Immune responses Lynch syndrome Microsatellite instability Biomedicine general Epidemiology Human Genetics Cancer Research
Content Type	Text
Resource Type	Article
Subject	Genetics Cancer Research Genetics (clinical) Oncology

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