title: Tetranucleotide repeats in coding regions: no evidence for involvement in EMAST carcinogenesis.
abstract: Genetic instability is a hallmark of malignancy. In the majority of malignant tumors, chromosomal instability leads to major numerical and structural chromosomal aberrations. In contrast, some tumors have a deficient DNA mismatch repair system and accumulate mutations particularly in repetitive mono- and dinucleotide sequences, a phenomenon referred to as microsatellite instability (MSI). Recently, a novel phenotype of tumors presenting with elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been reported. To date, not much is known about the molecular mechanisms of EMAST tumorigenesis. In MSI tumors, instability at specific mono- and dinucleotide repeats leads to alteration of genes carrying these repeats and thus may contribute to MSI tumorigenesis. We hypothesized that, similarly to the MSI phenotype, development of EMAST cancers may be promoted by mutations affecting tetranucleotides located in coding regions of the genome. To test this hypothesis, we performed a genome-wide database search to identify tetranucleotides in gene-encoding regions. Only seven tetranucleotide repeats located in predicted gene-encoding regions were retrieved. Allele length analysis yielded three remaining candidates with a monomorphic pattern in healthy individuals. Mutation analysis revealed that none of these three candidates displayed mutations in EMAST-positive bladder cancers. These data suggest that mutational inactivation of tetranucleotide-containing genes is very unlikely to contribute to the progression of EMAST tumors.
authors.affiliation: Institute of Molecular Pathology, University of Heidelberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kloor
authors.forename: Yvette
authors.initials: Y
authors.lastname: Schwitalle
authors.forename: Magnus
authors.initials: M
authors.lastname: von Knebel Doeberitz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D002869:Chromosome Aberrations; D030541:Databases, Genetic; D015894:Genome, Human; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D016366:Open Reading Frames / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor