PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines
Pollock, P.M., Walker, G.J., Glendening, J.M., Que Noy, T., Bloch, N.C., Fountain, J.W., & Hayward, N.K. (2002) PTEN inactivation is rare in melanoma tumours but occurs frequently in melanoma cell lines. Melanoma Research, 12(6), pp. 565-575.
Deletions detected in cytogenetic and loss of heterozygosity (LOH) studies indicate that at least one tumour suppressor gene maps to the long arm of chromosome 10. Previous deletion mapping studies have observed LOH on 10q in about 30% of melanomas analysed. The PTEN gene, mapping to chromosome band 10q23.3, encodes a protein with both lipid and protein phosphatase activity. Somatic mutations and deletions in have been detected in a variety of cell lines and tumours, including melanoma samples. We performed mutation analyses and extensive allelic loss studies to investigate the role this gene plays in melanoma pathogenesis. We found that a total of 34 out of 57 (60%) melanoma cell lines carried hemizygous deletions of chromosome 10q encompassing the PTEN locus. A further three cell lines carried smaller deletions excluding PTEN. Inactivation of both PTEN alleles by exon-specific homozygous deletion or mutation was observed in 13 out of 57 (23%) melanoma cell lines. The mutation spectrum observed does not indicate an important role for ultraviolet radiation in the genesis of these mutations, and evidence from three cell lines supports the acquisition of PTEN aberrations in culture. Ten out of 49 (20%) matched melanoma tumour/normal samples harboured hemizygous deletions of either the whole chromosome or most of the long arm. Mutations within were detected in only one of the 10 tumours demonstrating LOH at 10q23 that were analysed. These results suggest that PTEN inactivation may be important for the propagation of melanoma cells in culture, and that another chromosome 10 tumour suppressor gene may be important for melanoma pathogenesis.
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|Item Type:||Journal Article|
|Keywords:||Chromosomes, Human, Pair 10/genetics, Gene Amplification, Gene Deletion, Humans, Loss of Heterozygosity, Matched-Pair Analysis, Melanoma/ genetics, Microsatellite Repeats, PTEN Phosphohydrolase, Phosphoric Monoester Hydrolases/ genetics, Reverse Transcriptase Polymerase Chain Reaction, Skin Neoplasms/ genetics, Tumor Cells, Cultured, Tumor Suppressor Proteins/ genetics|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)|
|Divisions:||Past > Schools > Cell & Molecular Biosciences
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > Institutes > Institute of Health and Biomedical Innovation
|Deposited On:||09 Sep 2011 04:05|
|Last Modified:||09 Sep 2011 04:05|
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