title: Extensive somatic microsatellite mutations in normal human tissue.
abstract: Microsatellite (MS) instability occurs in tumors with DNA mismatch repair (MMR) deficiencies but is typically absent in adjacent normal tissue. However, MS mutations have been observed in normal tissues from rare individuals with congenital MMR deficiencies. Autopsy tissues from a 4-year-old with congenital MMR deficiency (MLH1-/-) were examined for MS mutations. Insertions and deletions were observed in CA-repeat MS loci. Approximately 0.26 to 1.4 mutations per MS locus per cell were estimated to be present in normal heart, lymph node, kidney, and bladder epithelium. These findings illustrate that phenotypically normal MMR-deficient cells commonly accumulate MS mutations. Loss of MMR and the accumulation of some MS mutations may occur early in MMR-deficient tumor progression, even before a gatekeeper mutation.
authors.affiliation: Department of Medical Genetics, University of Helsinki, FIN-00014 Helsinki, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Vilkki
authors.forename: J L
authors.initials: JL
authors.lastname: Tsao
authors.forename: A
authors.initials: A
authors.lastname: Loukola
authors.forename: M
authors.initials: M
authors.lastname: Pöyhönen
authors.forename: O
authors.initials: O
authors.lastname: Vierimaa
authors.forename: R
authors.initials: R
authors.lastname: Herva
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: D
authors.initials: D
authors.lastname: Shibata
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020137:Base Pair Mismatch; D001932:Brain Neoplasms / Q000235:genetics; D002352:Carrier Proteins; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005910:Glioma / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D000070957:MutL Protein Homolog 1; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D004247:DNA; D000070957:MutL Protein Homolog 1