SelTarbase, a database of human mononucleotide-microsatellite mutations and their potential impact to tumorigenesis and immunology
Open Access
- 9 October 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 38 (suppl_1), D682-D689
- https://doi.org/10.1093/nar/gkp839
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.Keywords
This publication has 31 references indexed in Scilit:
- Unregulated smooth-muscle myosin in human intestinal neoplasiaProceedings of the National Academy of Sciences of the United States of America, 2008
- A Mutant Allele ofMRE11Found in Mismatch Repair-deficient Tumor Cells Suppresses the Cellular Response to DNA Replication Fork Stress in a Dominant Negative MannerMolecular Biology of the Cell, 2008
- TCF-4 isoforms absent in TCF-4 mutated MSI-H colorectal cancer cells colocalize with nuclear CtBP and repress TCF-4-mediated transcriptionOncogene, 2006
- Finishing the euchromatic sequence of the human genomeNature, 2004
- Microsatellites: simple sequences with complex evolutionNature Reviews Genetics, 2004
- Conservation of mononucleotide repeats within 3′ and 5′ untranslated regions and their instability in MSI-H colorectal cancerOncogene, 2001
- Systematic identification of genes with coding microsatellites mutated in DNA mismatch repair-deficient cancer cellsInternational Journal of Cancer, 2001
- Frameshift peptide-derived T-cell epitopes: A source of novel tumor-specific antigensInternational Journal of Cancer, 2001
- Inactivation of the Type II TGF-β Receptor in Colon Cancer Cells with Microsatellite InstabilityScience, 1995
- Clues to the Pathogenesis of Familial Colorectal CancerScience, 1993