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Title: Somatic genetic changes in early lung carcinogenesis
Author: Chung, G. T. Y.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1996
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Carcinogenesis is a multistep process, and epithelial cancers are preceded by a series of morphologically recognisable pre-invasive lesions that develop over a period of time. Lung cancers arise from morphological steps involving hyperplasia, metaplasia, dysplasia, carcinoma in situ, invasive carcinoma and metastatic carcinoma. Chromosome 3 and p53 gene damage are two most common genetic abnormalities found in lung cancer. Loss of chromosome 3p and mutation of p53 gene occurred in severe dysplasia, a lesion believed to immediately precede invasive tumour. However, little is known about their involvement in early bronchial pre-invasive lesions. By studying different grades of pre-invasive lesions and tumours obtained from the same patient (parallel study), it was found that chromosome 3p loss and mutation of p53 gene occurred in early dysplastic lesions, suggesting that they were early events in the development of lung cancer. Moreover, damage to chromosome 3 was an earlier event than mutation of p53 gene. Sequential loss within chromosome 3p was observed. Chromosome 3p loss in invasive tumours was more frequent and more extensive than that in pre-invasive lesions. A study of pre-invasive lesions obtained over a period of nine months (longitudinal study) from a patient without tumour showed that there was a sequential damage of 3p, confirming the findings of the parallel study. In addition, the longitudinal study showed that there was a clonal expansion of p53 mutant cells over the nine-month period. Using microsatellite markers within a homozygously deleted region in a small lung cancer cell line, U2020, an interstitial deletion on 3p in dysplastic lesions was delineated which only partly overlaps the U2020 deletion. This suggested that allele loss study in pre-invasive lesions can potentially provide refinement to the location of tumour suppressor genes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available