title: A substantial proportion of microsatellite-unstable colon tumors carry TP53 mutations while not showing chromosomal instability.
abstract: Chromosomal instability in colon tumors implies the presence of numerical and structural chromosome aberrations and is further characterized by the absence of microsatellite instability and the occurrence of KRAS and/or TP53 mutations. In a previous screening of 194 colon tumors for both microsatellite instability and TP53 mutation, we found 25 microsatellite-unstable tumors, in 9 (36%) of which, presumed to be chromosomally stable, there were TP53 mutations. This prompted us to investigate whether a TP53 mutation in these microsatellite-unstable tumors would be an indicator of chromosomal instability, that is, whether this would be a category of tumors showing both microsatellite and chromosomal instability. For chromosomal instability assessment, we performed array-comparative genomic hybridization analysis of tumor and control DNA extracted from formalin-fixed, paraffin-embedded stage III colon tumor specimens. The array consisted of 435 subtelomere-specific BACs. We compared all but one (whose DNA was of bad quality) of the microsatellite-unstable TP53 mutation-containing tumors (8) with a similarly sized group of microsatellite-unstable tumors without TP53 mutation (11). Microsatellite-unstable tumors with a TP53 mutation showed on average 0.9 aberrations (range 0-3) when assessed with this array system. Those without a TP53 mutation showed on average 0.7 aberrations (range 0-2). Thus, microsatellite-unstable tumors showed few chromosomal abnormalities regardless of TP53 mutation status. Because, in our study, the microsatellite-stable tumors had on average 3.4chromosomal abnormalities (range 0-7), a clear difference exists between microsatellite-unstable and -stable tumors. Because a substantial proportion of microsatellite-unstable colon tumors carry a TP53 mutation while showing relativelyfewchromosomal aberrations, a TP53 mutation in these tumors cannot be considered to be an indicator of chromosomal instability.
authors.affiliation: Department of Medical Genetics, University of Groningen, The Netherlands.
authors.forename: Jantine L
authors.initials: JL
authors.lastname: Westra
authors.forename: Ludolf G
authors.initials: LG
authors.lastname: Boven
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Vlies
authors.forename: Hendrika
authors.initials: H
authors.lastname: Faber
authors.forename: Birgit
authors.initials: B
authors.lastname: Sikkema
authors.forename: Michael
authors.initials: M
authors.lastname: Schaapveld
authors.forename: Trijnie
authors.initials: T
authors.lastname: Dijkhuizen
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Charles H C M
authors.initials: CH
authors.lastname: Buys
authors.forename: John T M
authors.initials: JT
authors.lastname: Plukker
authors.forename: Klaas
authors.initials: K
authors.lastname: Kok
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
mesh_terms: D022202:Chromosomes, Artificial, Bacterial; D003110:Colonic Neoplasms / Q000235:genetics*; D016158:Genes, p53; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009154:Mutation