ORCID Profile
0000-0002-9910-7144
Current Organisation
Queen Mary University of London
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Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1038/MODPATHOL.2008.50
Abstract: The growth and metastasis of many cancers is due in part to loss of cell-cell adhesion. E-cadherin, plakoglobin and beta-catenin are important in cell adhesion. Our aim was to examine the presence of these molecules in Paget's disease of the vulva and Paget's disease of the breast, and to correlate any differences in their expression with the presence of invasive disease or an underlying carcinoma. Sixty-three archival cases of Paget's disease of the vulva, including eight associated with invasive disease, and 23 archival cases of Paget's disease of breast, which included 10 cases with ductal carcinoma in situ alone, four cases with both ductal carcinoma in situ and invasive carcinoma, and five cases with underlying invasive carcinoma alone, were analysed immunohistochemically for expression of E-cadherin, plakoglobin and beta-catenin proteins. The respective mRNAs were also detected by in situ hybridisation using digoxigenin-labelled cRNA probes. Seventy-six percent (41/54) of Paget's disease of vulva cases had >50% of Paget cells expressing the E-cadherin protein, compared with 28 % (2/7) of Paget's disease vulva with invasive disease. This result was significant, with a P-value of 0.039. Twenty-five percent (14/55) of the intraepidermal Paget's disease of the vulva cases had >50% of Paget cells expressing the plakoglobin protein, compared with 12% (1/8) of cases of Paget's disease of vulva with invasive disease, and for beta-catenin, 9% (5/55) of the non-invasive Paget's disease of the vulva had >50% of Paget cells expressing beta-catenin, compared with 12% (1/8) of Paget's disease of the vulva cases with invasive disease. Sixty-five percent (15/23) of the Paget's disease of the breast had >50% of Paget cells expressing E-cadherin, and for plakoglobin and beta-catenin it was 17% (4/23) and 28% (6/21), respectively. The results were not significant. The results suggest that reduced expression of E-cadherin may have a role to play in the pathogenesis of invasive Paget's disease of the vulva. Abnormal plakoglobin expression may be involved in the formation of some cases of Paget's of the vulva and the breast.
Publisher: Springer Science and Business Media LLC
Date: 09-2004
DOI: 10.1007/S10709-004-1930-X
Abstract: With the completion of the first draft of the human genome sequence, the next major challenge is assigning function to genes. One approach is genome-wide random chemical mutagenesis, followed by screening for mutant phenotypes of interest and subsequent mapping and identification of the mutated genes in question. We (a consortium made up of GlaxoSmithKline, the MRC Mammalian Genetics Unit and Mouse Genome Centre, Harwell, Imperial College, London, and the Royal London Hospital) have used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for use as animal models of human disease and for gene function assignment (Nolan et al., 2000). As of 2003, 35,000 mice have been produced to date in a genome-wide screen for dominant mutations and screened using a variety of screening protocols. Nearly 200 mutants have been confirmed as heritable and added to the mouse mutant catalogue and, overall, we can extrapolate that we have recovered over 700 mutants from the screening programme. For further information on the project and details of the data, see www.mgu.har.mrc.ac.uk/mutabase.
Publisher: Oxford University Press (OUP)
Date: 19-10-2017
DOI: 10.1111/BJD.15642
Publisher: Elsevier BV
Date: 11-2000
Publisher: Springer Science and Business Media LLC
Date: 12-1995
DOI: 10.1038/378789A0
Abstract: In Western Europe and the United States approximately 1 in 12 women develop breast cancer. A small proportion of breast cancer cases, in particular those arising at a young age, are attributable to a highly penetrant, autosomal dominant predisposition to the disease. The breast cancer susceptibility gene, BRCA2, was recently localized to chromosome 13q12-q13. Here we report the identification of a gene in which we have detected six different germline mutations in breast cancer families that are likely to be due to BRCA2. Each mutation causes serious disruption to the open reading frame of the transcriptional unit. The results indicate that this is the BRCA2 gene.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for David Kelsell.