Methylation-specific multiplex ligation-dependent probe amplification identifies promoter methylation events associated with survival in glioblastoma

DNA methylation plays an important role in cancer biology and methylation events are important prognostic and predictive markers in many tumor types. We have used methylation-specific multiplex ligation-dependent probe amplification to survey the methylation status of MGMT and 25 tumor suppressor ge...

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Bibliographic Details
Published in:Journal of neuro-oncology 2014-04, Vol.117 (2), p.243-251
Main Authors: Rankeillor, K. L., Cairns, D. A., Loughrey, C., Short, S. C., Chumas, P., Ismail, A., Chakrabarty, A., Lawler, S. E., Roberts, P.
Format: Article
Language:English
Subjects:
Adult
Aged
Brain Neoplasms - genetics
Brain Neoplasms - mortality
Clinical Study
DNA Methylation - genetics
Female
Genes, Tumor Suppressor
Glioblastoma - genetics
Glioblastoma - mortality
Humans
Kaplan-Meier Estimate
Male
Medicine
Medicine & Public Health
Middle Aged
Multiplex Polymerase Chain Reaction
Neurology
Oncology
Promoter Regions, Genetic - genetics
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Summary:DNA methylation plays an important role in cancer biology and methylation events are important prognostic and predictive markers in many tumor types. We have used methylation-specific multiplex ligation-dependent probe amplification to survey the methylation status of MGMT and 25 tumor suppressor genes in 73 glioblastoma cases. The data obtained was correlated with overall survival and response to treatment. The study revealed that methylation of promoter regions in TP73 (seven patients) , THBS1 (eight patients) and PYCARD (nine patients) was associated with improved outcome, whereas GATA5 (21 patients) and WT1 (24 patients) promoter methylation were associated with poor outcome. In patients treated with temozolomide and radiation MGMT and PYCARD promoter methylation events remained associated with improved survival whereas GATA5 was associated with a poor outcome. The identification of GATA5 promoter methylation in glioblastoma has not previously been reported. Furthermore, a cumulative methylation score separated patients into survival groups better than any single methylation event. In conclusion, we have identified specific methylation events associated with patient outcome and treatment response in glioblastoma, and these may be of functional and predictive/prognostic significance. This study therefore provides novel candidates and approaches for future prospective validation.
ISSN:0167-594X
1573-7373
DOI:10.1007/s11060-014-1372-y