Skewed Expression of the Genes Encoding Epigenetic Modifiers in High-Risk Uveal Melanoma
| Autor: | Geert W. Haasnoot, Naoimh Herlihy, Peter J. van den Elsen, T. Huibertus van Essen, Mehmet Dogrusöz, Marja C.J.A. van Eggermond, Martine J. Jager, J. William Harbour, Pieter A. van der Velden |
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| Přispěvatelé: | Pathology, CCA - Innovative therapy |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Uveal Neoplasms Monosomy Transcription Genetic Bisulfite sequencing Down-Regulation Biology Epigenesis Genetic Cellular and Molecular Neuroscience Gene expression Genes Regulator medicine Humans Epigenetics Gene Silencing Uvea Gene Melanoma Aged Genetics epigenetics Articles DNA Methylation Middle Aged medicine.disease Prognosis Sensory Systems eye diseases Gene Expression Regulation Neoplastic Ophthalmology Chromosome 3 Regulatory sequence DNA methylation oncology gene expression Disease Progression Female sense organs |
| Zdroj: | Investigative Ophthalmology & Visual Science, 56(3), 1447-1458 Investigative Ophthalmology and Visual Science, 56(3), 1447-1458 Herlihy, N, Dogrusoz, M, van Essen, T H, Harbour, J W, van der Velden, P A, van Eggermond, M C J A, Haasnoot, G W, van den Elsen, P J & Jager, M J 2015, ' Skewed Expression of the Genes Encoding Epigenetic Modifiers in High-Risk Uveal Melanoma ', Investigative Ophthalmology and Visual Science, vol. 56, no. 3, pp. 1447-1458 . https://doi.org/10.1167/iovs.14-15250 |
| ISSN: | 0146-0404 |
| DOI: | 10.1167/iovs.14-15250 |
| Popis: | Purpose Monosomy 3 (M3) or the presence of a specific RNA expression profile, known as class 2, is strongly associated with death from uveal melanoma (UM). Given the important role of epigenetic processes in cancer development and progression, we compared the transcriptional profiles of a selection of epigenetic regulators between primary UM with a good and a bad prognosis. Methods Transcriptional levels of 59 epigenetic regulator genes were measured by quantitative PCR (qPCR) in 20 UM, 12 with monosomy of chromosome 3 (M3) and 8 with disomy of chromosome 3 (D3). Validation was performed in an independent cohort. Expression levels were compared to clinicopathological characteristics, including class type. Bisulfite sequencing was used to evaluate the role of DNA methylation in gene silencing. Results In the first set of tumors, general downregulation of transcription of the genes encoding epigenetic regulatory enzymes was seen in association with M3. The 10 genes with the highest differential expression between M3 and D3 were selected and were analyzed in a second set of tumors. In the validation set, significantly lower levels of KAT2B (P = 0.008), HDAC11 (P = 0.009), KMT1C (P = 0.05), KDM4B (P = 0.003), KDM6B (P = 0.04), and BMI-1 (P = 0.001) transcripts were found in tumors with M3/class 2. Methylation of C-phosphate-G (CpG) residues was not observed on the putative regulatory regions of KAT2B, KDM4B, or KDM6B. Conclusions Expression levels of a number of histone-modifying genes and polycomb family members are significantly lower in uveal melanoma with monosomy 3/class 2, supporting a general dysregulation of epigenetic modifiers in UM with a bad prognosis. |
| Databáze: | OpenAIRE |
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