title: Microsatellite instability in childhood rhabdomyosarcoma is locus specific and correlates with fractional allelic loss.
abstract: Replication errors (RERs) were initially identified in hereditary nonpolyposis colon cancer and other tumors of Lynch syndrome II. Mutations in genes involved in mismatch repair give rise to a mutator phenotype, resulting in RERs. The mutator phenotype is thought to predispose to malignant transformation. Here we show that in the embryonal form of childhood rhabdomyosarcoma, RERs also occur, but in contrast to hereditary nonpolyposis colon cancer, only a subset of the microsatellite loci analyzed show RERs. The occurrence of RERs is strongly correlated with increased fractional allelic loss (P < 0.001), suggesting that the occurrence of RERs is a secondary phenomenon in rhabdomyosarcoma. Coincidental loss of genes involved in mismatch repair, possibly due to their proximity to tumor suppressor genes involved in tumor progression of embryonal form of childhood rhabdomyosarcoma, could explain the observed phenomenon.
authors.affiliation: Neurozintuigen Laboratory, Emma Kinderziekenhuis, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Visser
authors.forename: J
authors.initials: J
authors.lastname: Bras
authors.forename: C
authors.initials: C
authors.lastname: Sijmons
authors.forename: P
authors.initials: P
authors.lastname: Devilee
authors.forename: L C
authors.initials: LC
authors.lastname: Wijnaendts
authors.forename: J C
authors.initials: JC
authors.lastname: van der Linden
authors.forename: P A
authors.initials: PA
authors.lastname: Voûte
authors.forename: F
authors.initials: F
authors.lastname: Baas
mesh_terms: D000483:Alleles; D002648:Child; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D004261:DNA Replication; D004276:DNA, Satellite / Q000235:genetics*; D018450:Disease Progression; D005819:Genetic Markers; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009362:Neoplasm Metastasis; D012008:Recurrence; D018233:Rhabdomyosarcoma, Embryonal / Q000209:etiology / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D004276:DNA, Satellite; D005819:Genetic Markers