4th EUTROC, Liverpool, UK

Histological and molecular sub-types of ovarian cancer

Dr Jozien Helleman – Erasmus Medical Centre, Rotterdam, Netherlands


A lot of ovarian cancer cell lines are being used in in vitro studies but really the origin is very poorly defined so there is now more and more knowledge about different histological types and molecular sub-types within ovarian cancer. So that’s really a very heterogeneous disease that has different prognoses and we have a lot of cell lines that are available publically but nobody really knows which sub-type they represent. We did a study in forty ovarian cancer cell lines that are publically available and we characterised them to identify which are really, for instance, high grade serous or low grade serous or endometrioid or clear cell. So we now looked at a different kind of data; we have expression data and micro-RNA expression and we did sequencing of about 2,000 cancer related genes. While combining all this data and also looking at therapy response, you can say something about which histological type they represent. The next step will be to look at the molecular sub-type which they represent.

What data is collected when classifying tumour sub-types?

The first step now is to have an idea of what kind of cell lines are we looking at, what are they modelling? Then you can select the cell lines that model, for instance, high grade serous and then look at can you find markers that predict response to therapy or other things, anything you can imagine.

Is there a move towards personalised medicine in this field?

Yes, indeed. Why we started with this study was to look at markers for the prediction of response to therapy but we came across that the origin of the cell lines is very poorly defined so we looked into that. Now it turns out to be that it’s a very heterogeneous set and it would be better to focus, maybe, on one group and then do this analysis. So this is what came along but our project will next focus on finding biomarkers so these can be used, indeed, to personalise therapy.

Are there any other studies similar to this?

There might be other similar studies but smaller sets and what makes this more unique is that we really focussed on this and the cell lines are all cultured very uniquely so you can compare them very well. Because if you change culture media or conditions then you get different gene expression, for instance, so things can change.

What is the goal of the study?

The main goal is indeed to get to personalised therapy and you need a model for ovarian cancer to say how different subtypes react on specific drugs. That’s something you cannot start testing in patients so that’s where these cell lines come in. Yes, it’s a model system for that and you can find… well, the first set-up would be to have all the cell lines tested for eight chemotherapeutics and then see which are responsive, which are not and compare the gene expression, for instance, the sequencing data, and then find biomarkers. Another part could be now we have identified the different sub-types you can look sub-type specific, whether you have specific characteristics that can be targets for novel therapies and maybe things that sensitise to the standard chemotherapy or novel therapies that really target these sub-types.