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Analysis of CHK2 in vulval neoplasia.

Reddy, A; Yuille, M; Sullivan, A; Repellin, C; Bell, A; Tidy, JA; Evans, DJ; ... Crook, T; + view all (2002) Analysis of CHK2 in vulval neoplasia. Br J Cancer , 86 (5) pp. 756-760. 10.1038/sj.bjc.6600131.

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Abstract

Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia. We identified the previously described silent polymorphism at codon 84 (A>G at nucleotide 252) in the germ-line of six out of 72, and somatic mutations in two out of 40 cases of vulval squamous cell carcinomas and none of 32 cases of vulval intraepithelial neoplasia. One mutation introduced a premature stop codon in the kinase domain of CHK2, whereas the second resulted in an amino acid substitution in the kinase domain. The two squamous cell carcinomas with mutations in CHK2 also expressed mutant p53. A CpG island was identified close to the putative CHK2 transcriptional start site, but methylation-specific PCR did not detect methylation in any of 40 vulval squamous cell carcinomas, irrespective of human papillomavirus or p53 status. Consistent with this observation, no cancer exhibited loss of CHK2 expression at mRNA or protein level. Taken together, these observations reveal that genetic but not epigenetic changes in CHK2 occur in a small proportion of vulval squamous cell carcinomas.

Type: Article
Title: Analysis of CHK2 in vulval neoplasia.
Location: England
DOI: 10.1038/sj.bjc.6600131
Keywords: Adult, Carcinoma, Squamous Cell, Checkpoint Kinase 2, DNA Methylation, DNA Primers, DNA, Neoplasm, Female, Gene Expression Regulation, Neoplastic, Humans, Papillomaviridae, Papillomavirus Infections, Polymerase Chain Reaction, Protein Kinases, Protein-Serine-Threonine Kinases, RNA, Messenger, Tumor Virus Infections, Vulvar Neoplasms
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
URI: http://discovery.ucl.ac.uk/id/eprint/1484731
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