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CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

By Anthony L. Cook, Pamela M. Pollock, John Welch, Michael D. Walsh, Rayleen V. Bowman, Kathryn C. Baumann, Nicholas K. Hayward and J. Helen Leonard

Abstract

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb. Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC and MCC, we wished to determine if this was also the case in MCC. Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and 1 on 9q. No loss of heterozygosity (LOH) was seen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p. Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined. Half of all informative cases had LOH at D9S168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168. A second region (IFNA-D9S126) showed LOH in 10 (44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all 11 tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p14(ARF) antibody. These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus

Topics: 111201 Cancer Cell Biology, Blotting, Western, Carcinoma, Merkel Cell/ genetics, Chromosome Aberrations, Chromosomes, Human, Pair 9/ genetics, Cyclin-Dependent Kinase Inhibitor p16/ genetics/metabolism, Gene Deletion, Heterozygote, Homozygote, Humans, Immunoenzyme Techniques, Loss of Heterozygosity, Microsatellite Repeats, Mutation, Proteins/genetics/metabolism, Skin Neoplasms/ genetics, Tumor Suppressor Protein p14ARF
Publisher: John Wiley & Sons Inc
Year: 2001
DOI identifier: 10.1002/ijc.1352
OAI identifier: oai:eprints.qut.edu.au:45816
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