Data di Pubblicazione:
2015
Citazione:
Genome-wide DNA methylation profiling of recurrent and non-recurrent chordomas / A. Alholle, A.T. Brini, J. Bauer, S. Gharanei, S. Niada, A. Slater, D. Gentle, E.R. Maher, L. Jeys, R. Grimer, V.P. Sumathi, F. Latif. - In: EPIGENETICS. - ISSN 1559-2294. - 10:3(2015 Mar), pp. 213-220. [10.1080/15592294.2015.1006497]
Abstract:
Chordomas are an aggressive rare type of malignant bone tumors arising from the remnant of the notochord.
Chordomas occur mainly in vertebral bones and account for 1–4% of malignant bone tumors. Management and
treatment of chordomas are difficult as they are resistant to conventional chemotherapy; therefore, they are mainly
treated with surgery and radiation therapy. In this study, we performed DNA methylation profiling of 26 chordomas and
normal nucleus pulposus samples plus UCH-1 chordoma cell line using the Illumina Infinium HumanMethylation450
BeadChips. Combined bisulfite restriction analysis and bisulfite sequencing was used to confirm the methylation data.
Gene expression was analyzed using RT-PCR before and after 5-aza-2’-deoxycytidine (5-azaDC) treatment of chordoma
cell lines. Analysis of the HumanMethylation450 BeadChip data led to the identification of 8,819 loci (2.9%) that were
significantly differentially methylated (>0.2 average b-value difference) between chordomas and nucleus pulposus
samples (adjusted P < 0.05). Among these, 5,868 probes (66.5%) were hypomethylated, compared to 2,951 (33.5%) loci
that were hypermethylated in chordomas compared to controls. From the 2,951 differentially hypermethylated probes,
33.3% were localized in the promoter region (982 probes) and, among these, 104 probes showed cancer-specific
hypermethylation. Ingenuity Pathway Analysis indicates that the cancer-specific differentially methylated loci are
involved in various networks including cancer disease, nervous system development and function, cell death and
survival, cellular growth, cellular development, and proliferation. Furthermore, we identified a subset of probes that
were differentially methylated between recurrent and non-recurrent chordomas. BeadChip methylation data was
confirmed for these genes and gene expression was shown to be upregulated in methylated chordoma cell lines after
treatment with 5-azaDC. Understanding epigenetic changes in chordomas may provide insights into chordoma
tumorigenesis and development of epigenetic biomarkers.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
chordomas; DNA Methylation; HumanMethylation450 BeadChips; recurrent; non-recurrent
Elenco autori:
A. Alholle, A.T. Brini, J. Bauer, S. Gharanei, S. Niada, A. Slater, D. Gentle, E.R. Maher, L. Jeys, R. Grimer, V.P. Sumathi, F. Latif
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