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Medical Research Council Clinical Oncology and Radiotherapeutics Unit, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH [G. T. Y. C., V. S., P. H. R.]; Department of Pathology, Regional Cardiothoracic Centre, Wythenshawe Hospital, Clay Lane, Wythenshawe, Manchester M23 9LT [P. H.]; and The London Chest Hospital, Bonner Road, London E2 9JX [R. R., R. T.], United Kingdom
Lung tumors, particularly squamous cell carcinomas, are believed to develop through a series of morphological abnormalities, driven by underlying somatic genetic changes. One way of studying this process is to analyze candidate somatic genetic changes in samples of squamous metaplasia and bronchial dysplasia of varying degrees of severity as well as tumor from the same patient. This assumes a clonal relationship between these lesions. In this article, we provide evidence that adjacent, physically distinct bronchial abnormalities are clonally related. This has been achieved using a plaque assay technique to detect the same p53 mutation, present throughout a tumor specimen, in a small proportion of cells in an adjacent squamous metaplasia. In addition, we have obtained two dysplasia samples from a tumor-free patient over a 9-month interval. The earlier sample had one p53 mutation, whereas the later sample had two p53 mutations on different allels. Thus, the pattern of clonal evolution detected in the parallel samples mimics the pattern seen in longitudinal samples and supports the analysis of synchronously collected samples for the study of tumor progression.
1 Supported by the Croucher Foundation.
2 Recipient of a Medical Research Council Clinical Scientist Fellowship.
3 To whom requests for reprints should be addressed. Phone: +44 (1223) 402412; Fax: +44 (1223) 402180.
Received 9/26/95. Accepted 2/ 1/96.
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