A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting

Abstract

Embryonal rhabdomyosarcomas (malignant pediatric tumors of striated muscle origin) have been shown to arise from cells that are clonally isodisomic for loci on chromosome 11p. We determined the parental origin of alleles in this genomic region in familial and sporadic cases of this disease and found that isodisomic chromosome 11p alleles in each tumor were of paternal origin. We have developed a modification of Knudson's two-hit model from these data that is capable of explaining the preferential allele retention and of resolving the apparent contradiction between such specific and early events in several embryonal tumors and discrepancies in the inheritance of predisposition in some of these diseases.