The c-met proto-oncogene encodes a tyrosine kinase receptor for hepatocyte growth factor/scatter factor. Losses of c-met alleles have been documented in human carcinomas. In breast carcinoma c-met has been suggested to be a potential inactivated tumour suppressor gene (TSG). In non-small cell lung carcinoma (NSCLC) a general reduction of c-met expression in squamous cell carcinomas (SQCCs), as well as overexpression in adenocarcinomas (ADCs) have been revealed. Furthermore, many SQCCs and ADCs had undetectable c-met mRNA and protein. These results prompted us to explore c-met allelic alterations in NSCLC. Our main goal was to address the possible involvement of inactivated c-met alleles in the development and progression of NSCLC. In this LOH analysis two polymorphic-sensitive probes corresponding to the c-met gene, p-metH and p-metD, were used to analyze normal and tumour DNA samples from patients with primary NSCLC. Of 110 cases examined with p-metH, 56 (50.9%) were informative and 4 (7.1%) exhibited LOH. Among 109 patients examined with p-metD, 28 (25.7%) were informative and 1 (3.6%) was LOH-positive. The combined LOH incidence for c-met was 7.4% (5/68 informative cases). Lastly, since a locus adjacent (distally) to c-met on chromosome 7, D7S95, was shown to exhibit a significant LOH frequency in gastric carcinoma (43.3%), we also sought to determine if loss of this locus was common in NSCLC. Of 104 patients examined at D7S95, 45 (43.3%) were informative and 1 (2.2%) exhibited LOH. These findings suggest, firstly, that c-met does not have a possible role as an inactivated TSG in the tumourigenesis of NSCLC nor is it closely linked to a putative TSG, and secondly, D7S95 does not contain a detectable inactivated TSG or a closely-mapping TSG in NSCLC.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.27322 |
| Date | January 1996 |
| Creators | Gebien, Darryl Jordan. |
| Contributors | Zhu, Hong (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 Pathology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001549784, proquestno: MQ29697, Theses scanned by UMI/ProQuest. |
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