Von Recklinghausen neurofibromatosis (NF1) and neurofibromatosis type 2 (NF2) are autosomal dominant inherited disorders which predispose carriers to various benign and malignant tumours. Both genes are thought to act as tumour suppressors with inactivation of both alleles resulting in abnormal cell growth. By inference from other hereditary cancer syndromes, it has been hypothesized that somatic mutation at the NF1 and NF2 loci is involved in the development of sporadic tumors of the types found with increased prevalence in these disorders. / In addition to other malignancies, individuals with NF1 are at an increased risk to develop astrocytomas and rhabdomyosarcomas. We have therefore screened 34 astrocytomas for loss of heterozygosity (LOH) using three NF1-derived cDNA probes, and have found no abnormalities. / Half of NF2 patients develop spinal and cranial meningiomas, while fully 90% develop bilateral vestibular schwannomas. In addition, loss of heterozygosity (LDH) of chromosome 22 markers is known to occur in malignant melanona and breast cancer. To evaluate the role of NF2 in sporadic cancer, single-stranded conformation polymorphism analysis (SSCP) was carried out on all 17 exons of the NF2 gene. 57 variants have been found, 44 in meningiomas, 12 in schwannomas, and a single variant in a melanoma. / Most of these represent inactivating mutations (frameshift, splice-site, and nonsense), as determined by direct sequencing. Since the majority of these changes occur in tumours previously shown to have LOH at chromosome 22 markers flanking NF2, our results support a tumour suppressor role for this gene in meningiomas. In addition, given that 40% of our tumours do not show LOH over this region, we propose that at least one other gene is involved in the development of this latter subset of meningiomas. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.22793 |
| Date | January 1995 |
| Creators | Rangaratnam, Shyam |
| Contributors | Narod, Steven A. (advisor), Rosenblatt, David (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 Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001462340, proquestno: MM05617, Theses scanned by UMI/ProQuest. |
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