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Genomic evidence of pre-invasive clonal expansion, dispersal and progression in bronchial dysplasia

McCaughan, F; Pipinikas, CP; Janes, SM; George, PJ; Rabbitts, PH; Dear, PH; (2011) Genomic evidence of pre-invasive clonal expansion, dispersal and progression in bronchial dysplasia. J PATHOL , 224 (2) 153 - 159. 10.1002/path.2887.

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Abstract

The term 'field cancerization' is used to describe an epithelial surface that has a propensity to develop cancerous lesions, and in the case of the aerodigestive tract this is often as a result of chronic exposure to carcinogens in cigarette smoke [1,2]. The clinical endpoint is the development of multiple tumours, either simultaneously or sequentially in the same epithelial surface. The mechanisms underlying this process remain unclear; one possible explanation is that the epithelium is colonized by a clonal population of cells that are at increased risk of progression to cancer. We now address this possibility in a short case series, using individual genomic events as molecular biomarkers of clonality. In squamous lung cancer the most common genomic aberration is 3q amplification. We use a digital PCR technique to assess the clonal relationships between multiple biopsies in a longitudinal bronchoscopic study, using amplicon boundaries as markers of clonality. We demonstrate that clonality can readily be defined by these analyses and confirm that field cancerization occurs at a pre-invasive stage and that pre-invasive lesions and subsequent cancers are clonally related. We show that while the amplicon boundaries can be shared between different biopsies, the degree of 3q amplification and the internal structure of the 3q amplicon varies from lesion to lesion. Finally, in this small cohort, the degree of 3q amplification corresponds to clinical progression. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Type: Article
Title: Genomic evidence of pre-invasive clonal expansion, dispersal and progression in bronchial dysplasia
DOI: 10.1002/path.2887
Keywords: clonality, bronchial dysplasia, molecular copy-number counting, SQUAMOUS-CELL CARCINOMAS, LUNG-CANCER, FIELD CANCERIZATION, 3Q AMPLIFICATION, RESOLUTION, SOX2, CARCINOGENESIS, BREAKPOINTS, EPITHELIUM, ONCOGENE
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
URI: http://discovery.ucl.ac.uk/id/eprint/1304803
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