Rhabdomyosarcoma is a class of malignant neoplasms composed of cells histologically resembling fetal striated muscle. It is the most common soft tissue tumor of children, adolescents, and young adults. In this Thesis, I demonstrate that the rhabdomyosarcoma tumor class is delimited in molecular genetic terms by the expression of the MyoD gene, and that loss of alleles on chromosome 11 distinguishes between the embryonal and alveolar subtypes. The elucidation of this genotypic distinction resolved the paradox between phenotypic variation and an apparent histogenetic relatedness between and among rhabodmyosarcomas. It also allowed for the construction of a two-tiered scheme for the unequivocal differential diagnosis of rhabdomyosarcoma and its subtypes. MyoD is syntenic to but distinct from Rd, a locus consistently involved in the etiology of the embryonal subtype. Abnormal segregation of alleles on chromosome 11p in both familial and sporadic embryonal rhabdomyosarcoma results in retention of only paternal alleles in tumors and supports a model of tumorigenesis involving unlinked modifier loci which inactivate Rd, perhaps by genome imprinting. Uniform loss of heterozygosity at loci on chromosome 11 in phenotypic variants of embryonal rhabdomyosarcoma that show simultaneous differentiation into another neoplastic tissue type implies that mutation at Rd is one of the earliest somatic events.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74265 |
| Date | January 1989 |
| Creators | Scrable, Heidi |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001069258, proquestno: AAINN63428, Theses scanned by UMI/ProQuest. |
Page generated in 0.0021 seconds