Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome
- 2 December 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Familial Cancer
- Vol. 9 (2), 173-179
- https://doi.org/10.1007/s10689-009-9307-z
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.Keywords
This publication has 26 references indexed in Scilit:
- A systematic review of humoral immune responses against tumor antigensCancer Immunology, Immunotherapy, 2009
- Feasibility of Screening for Lynch Syndrome Among Patients With Colorectal CancerJournal of Clinical Oncology, 2008
- Characterization of humoral immune responses against p16, p53, HPV16 E6 and HPV16 E7 in patients with HPV‐associated cancersInternational Journal of Cancer, 2008
- Immunology and the Lynch SyndromeGastroenterology, 2008
- Immune Response Against Frameshift-Induced Neopeptides in HNPCC Patients and Healthy HNPCC Mutation CarriersGastroenterology, 2008
- Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of CancerJournal of Proteome Research, 2008
- Risk of colorectal and endometrial cancer for carriers of mutations of the hMLH1 and hMSH2 gene: correction for ascertainmentJournal of Medical Genetics, 2005
- Spontaneous Tumor-Specific Humoral and Cellular Immune Responses to NY-ESO-1 in Hepatocellular CarcinomaClinical Cancer Research, 2004
- Pathogenesis of DNA repair-deficient cancers: a statistical meta-analysis of putative Real Common Target genesOncogene, 2003
- High Prevalence of Activated Intraepithelial Cytotoxic T Lymphocytes and Increased Neoplastic Cell Apoptosis in Colorectal Carcinomas with Microsatellite InstabilityThe American Journal of Pathology, 1999