Nucleic Acids Research Advance Access published online on October 9, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp839
Database Issue |
SelTarbase, a database of human mononucleotide-microsatellite mutations and their potential impact to tumorigenesis and immunology
1Institute for Clinical Chemistry, Medical Faculty of Mannheim of the University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, 2Applied Tumorbiology, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 220/221, D–69120 Heidelberg, 3Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstr. 1, D–69117 Heidelberg and 4Central Unit Biostatistics, German Cancer Research Center, Im Neuenheimer Feld 280, D–69120 Heidelberg, Germany
*To whom correspondence should be addressed. Tel: +49 621 383 3561; Fax: +49 621 383 73 3561; Email: stefan.woerner{at}medma.uni-heidelberg.de; admin{at}seltarbase.org
Received July 28, 2009. Revised September 19, 2009. Accepted September 21, 2009.
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.