Wilms' tumor is an embryonal malignancy of the kidney that affects approximately 1 in 10,000 children under the age of 5 years. These tumors arise from the metanephric blastemal cells that do not follow the normal course of cellular differentiation, but instead continue along the path of proliferation. A Wilms' tumor predisposing gene, WT1, situated at 11p13 has been cloned and spans 50 kb of genomic DNA. It encodes a putative transcription factor, with an NH$ sb2$-terminus rich in proline and glutamine residues and a COOH-terminus composed of four zinc fingers of the Cys$ sb2$-His$ sb2$ type. The WT1 gene is alternatively spliced, giving rise to four mRNA and protein isoforms, encoding polypeptides ranging in size from 45-49 kDa. Although some Wilms' tumors occur in familial setting (1-2%), most cases occur as a sporadic form. Of the sporadic tumors analyzed to date for WT1 mutations, only the zinc finger domains have been evaluated.We have investigated the status of the complete WT1 gene in 101 tumors to document the frequency with which WT1 is mutated in sporadic and hereditary Wilms' tumors. We have identified homozygous, hemizygous and heterozygous mutations in 10 tumors, of which 7 were found to occur within the zinc finger domain. Our results indicate that the frequency of mutations (insertions, deletions, base substitutions) in sporadic tumors is $ sim$6%. We have been able to identify novel mutations in addition to already documented ones.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.26168 |
| Date | January 1994 |
| Creators | Varanasi, Ramani |
| Contributors | Pelletier, J. (advisor) |
| 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 | Master of Science (Department of Biochemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001482452, proquestno: MM94537, Theses scanned by UMI/ProQuest. |
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