Open AccessA model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting.
Author(s) -
Heidi Scrable,
Webster K. Cavenee,
Fereshteh Ghavimi,
Mark A. Lovell,
Kenneth Morgan,
Carmen Sapienza
Publication year - 1989
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.86.19.7480
Subject(s) - biology , allele , genetics , carcinogenesis , genomic imprinting , imprinting (psychology) , rhabdomyosarcoma , chromosome , cancer research , cancer , gene , sarcoma , pathology , medicine , dna methylation , gene expression
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.