OGT's high-throughput service helps to identify new ovarian cancer markers

Tuesday 23 August 2011

Researchers at Imperial College’s Faculty of Medicine are using OGT’s high throughput microarray screening service to help them investigate DNA methylation patterns as potential biomarkers in ovarian cancer.

The Division of Surgery, Oncology, Reproductive Biology and Anaesthetics at Imperial College is investigating the links between DNA methylation and development of ovarian cancer. This work, funded by Cancer Research UK and Ovarian Cancer Action, is focusing on changes in DNA methylation before and after treatment, and how this relates to the development of drug resistance. Professor Robert Brown, Chair in Translational Oncology in the Division, explained: “The long term aim of this project is to establish how changes in DNA methylation patterns and associated epigenetic silencing of gene expression can lead to tumour progression, and to identify biomarkers that can help to direct clinicians towards the most effective treatment for a given patient. There is a growing body of evidence to suggest that methylation patterns are highly significant in the development of cancers such as ovarian cancer, as well as being a driving force behind the acquisition of drug resistance during tumour recurrence, and we are hoping to understand these processes on a level that will directly impact on improving the treatment of patients.”

“For this type of study it is crucial that we use sufficiently large numbers of tumour samples, to identify meaningful statistical significance in the data and validate potential methylation markers. Concentrating on just specific regions of interest – in this case CpG rich regions – is one way of reducing the resources and manpower required, and we are using OGT’s screening service to help us with this focused approach. We worked closely with OGT’s bioinformaticians to help design the studies and optimise the features to focus on. We began working with OGT just over a year ago and, in the first phase of the study, performed a small investigation using cell model systems to look at the reproducibility of the data we obtained, and to evaluate the technology according to known methylation patterns in these models.

Analysis of this preliminary study took several months and, during this time, we changed the design of the arrays to more precisely focus on the regions we were investigating, and determine how best to analyse this type of methylation data. Using this new array design, we are now in the first biomarker validation phase of the project, providing OGT with processed DNA samples, which are subsequently labelled and hybridised onto the arrays. The raw data and images generated from the screens are then returned to us for analysis, ensuring complete transparency in the way the data is analysed and interpreted.”

“We have a very good relationship with the staff at OGT; there is a continual dialogue between the laboratories providing the samples, our researchers and OGT’s bioinformaticians. This is a very important aspect of the service OGT provides, and is key to understanding the in vivo functions of potential biomarkers we are identifying in the context of tumour development. We are hoping to work even more closely with OGT in the future, collaborating on development of new methodologies for investigation of DNA methylation.”

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