MICROSATELLITE INSTABILITY IN CHILDHOOD RHABDOMYOSARCOMA IS LOCUS-SPECIFIC AND CORRELATES WITH FRACTIONAL ALLELIC LOSS

Replication errors (RERs) were initially identified in hereditary nonp olyposis 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 Re show that in the embryonal form of childhood rhabdomyosarcoma, RERs also occur, but in contrast to heredi tary nonpolyposis colon cancer, only subset of the microsatellite loci analyzed show RERs, The occurrence of RERs is strongly correlated wit h increased fractional allelic loss (P < 0.001), suggesting that the o ccurrence of RERs is a secondary phenomenon in rhabdomyosarcoma, Coinc idental loss of genes involved in mismatch repair, possibly due to the ir proximity to tumor suppressor genes involved in tumor progression o f embryonal form of childhood rhabdomyosarcoma, could explain the obse rved phenomenon.