Source:http://linkedlifedata.com/resource/pubmed/id/19957108
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2010-5-17
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1573-7292
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pubmed:author |
pubmed-author:FindeisenPeterP,
pubmed-author:GarbeYvetteY,
pubmed-author:GermannAnjaA,
pubmed-author:Holinski-FederElkeE,
pubmed-author:KloorMatthiasM,
pubmed-author:MorakMonikaM,
pubmed-author:NeumaierMichaelM,
pubmed-author:ReuschenbachMiriamM,
pubmed-author:TariverdianMirjamM,
pubmed-author:WentzensenNicolasN,
pubmed-author:von Knebel DoeberitzMagnusM
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pubmed:issnType |
Electronic
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
173-9
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pubmed:meshHeading |
pubmed-meshheading:19957108-Antibodies,
pubmed-meshheading:19957108-Colorectal Neoplasms,
pubmed-meshheading:19957108-Colorectal Neoplasms, Hereditary Nonpolyposis,
pubmed-meshheading:19957108-Frameshift Mutation,
pubmed-meshheading:19957108-Humans,
pubmed-meshheading:19957108-Microsatellite Instability,
pubmed-meshheading:19957108-Microsatellite Repeats,
pubmed-meshheading:19957108-MutS Homolog 2 Protein,
pubmed-meshheading:19957108-Peptides
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pubmed:year |
2010
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pubmed:articleTitle |
Serum antibodies against frameshift peptides in microsatellite unstable colorectal cancer patients with Lynch syndrome.
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pubmed:affiliation |
Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220, 69120, Heidelberg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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