title: SelTarbase, a database of human mononucleotide-microsatellite mutations and their potential impact to tumorigenesis and immunology.
abstract: About 15% of human colorectal cancers and, at varying degrees, other tumor entities as well as nearly all tumors related to Lynch syndrome are hallmarked by microsatellite instability (MSI) as a result of a defective mismatch repair system. The functional impact of resulting mutations depends on their genomic localization. Alterations within coding mononucleotide repeat tracts (MNRs) can lead to protein truncation and formation of neopeptides, whereas alterations within untranslated MNRs can alter transcription level or transcript stability. These mutations may provide selective advantage or disadvantage to affected cells. They may further concern the biology of microsatellite unstable cells, e.g. by generating immunogenic peptides induced by frameshifts mutations. The Selective Targets database (http://www.seltarbase.org) is a curated database of a growing number of public MNR mutation data in microsatellite unstable human tumors. Regression calculations for various MSI-H tumor entities indicating statistically deviant mutation frequencies predict TGFBR2, BAX, ACVR2A and others that are shown or highly suspected to be involved in MSI tumorigenesis. Many useful tools for further analyzing genomic DNA, derived wild-type and mutated cDNAs and peptides are integrated. A comprehensive database of all human coding, untranslated, non-coding RNA- and intronic MNRs (MNR_ensembl) is also included. Herewith, SelTarbase presents as a plenty instrument for MSI-carcinogenesis-related research, diagnostics and therapy.
authors.affiliation: Medical Faculty of Mannheim, Institute for Clinical Chemistry, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. stefan.woerner@medma.uni-heidelberg
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Woerner
authors.forename: Yan P
authors.initials: YP
authors.lastname: Yuan
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Sebastian
authors.initials: S
authors.lastname: Korff
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods* / Q000639:trends; D004260:DNA Repair; D030541:Databases, Genetic; D030561:Databases, Nucleic Acid; D006801:Humans; D007107:Immune System / Q000378:metabolism*; D016247:Information Storage and Retrieval / Q000379:methods; D020407:Internet; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D012984:Software