High frequency of submicroscopic hemizygous deletion is a major mechanism of loss of expression of PTEN in uveal melanoma
| Autor: | Mohamed H. Abdel-Rahman, Ying Yang, Frederick H. Davidorf, Charis Eng, Xiao Ping Zhou, Elson L. Craig |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Uveal Neoplasms Cancer Research Pathology medicine.medical_specialty Tumor suppressor gene Loss of Heterozygosity Biology Polymerase Chain Reaction Loss of heterozygosity medicine PTEN Humans Genotyping Melanoma Aged Aged 80 and over PTEN Phosphohydrolase Middle Aged medicine.disease Immunohistochemistry Oncology Mutation Cancer research biology.protein Female Immunostaining Gene Deletion Comparative genomic hybridization |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 24(2) |
| ISSN: | 1527-7755 |
| Popis: | PurposeAlthough cytogenetic aberrations at 10q have been reported in up to 27% of uveal melanomas, the role of PTEN in the pathogenesis of uveal melanoma is largely unknown. Our aim was to determine the frequency and clinical significance of PTEN alterations in uveal melanomas.Patients and MethodsWe examined PTEN expression using immunohistochemistry in 75 sporadic uveal melanomas, with an average follow-up of 89 months. Molecular cytogenetic alterations were studied using comparative genomic hybridization (CGH). Genotyping was carried out using an intragenic PTEN marker and two flanking markers. Mutational analysis of PTEN was also carried out.ResultsOf the 75 tumors, 12 (16%) showed no PTEN immunostaining, 32 (42.7%) showed weak to moderate staining and the remaining 31 (38.2%) showed staining similar to the normal internal controls. Using CGH, only two (15.4%) of 13 samples showed any loss of 10q. However, in the 38 tumors with informative genotyping, we found that 29 (76.3%) had loss of heterozygosity (LOH) of at least one PTEN marker, and 15 (39.5%) showed LOH of at least two markers. Mutations in the coding region of PTEN were identified in four (11.4%) of 35 tumors. Further, loss of cytoplasmic PTEN expression by immunohistochemistry was associated with shortened disease-free survival (P = .029).ConclusionThis is the first demonstration that PTEN is a tumor suppressor involved in uveal melanoma pathogenesis and may be associated with clinical outcome. Our data also suggest that submicroscopic deletion, but not large deletions, is the major mechanism of loss of PTEN expression in uveal melanomas. |
| Databáze: | OpenAIRE |
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