European Multidisciplinary Conference in Thoracic Oncology (EMCTO) 2013

Next generation sequencing in oncology

Dr Antonio Marchetti – University-Foundation, Chieti, Italy
 

Antonio, you’re concerned with molecular predictive medicine, in fact you’re Director of Predictive Medicine at your university. Next generation sequencing is all the rage now, everybody’s talking about this amazing power to look at the genome, but what can it actually do in oncology?

Next generation sequencing is an extremely powerful technology that allows you to sequence thousands and thousands of genes simultaneously with a limited cost for a single sequence. So it’s a revolution consisting in the power of this technical approach together with a low cost of the single sequences. Next generation sequencing can be used for different purposes in oncology. First of all it’s been used for genome-wide analysis, that means the analysis of thousands and thousands of genomes.

That’s pretty complex, though, isn’t it?

Pretty complex, it’s generally complex.

You get a lot of information.

Yes, a lot of information and data analysis is one of the main limitations now of this technology.

Do you get too much information?

Maybe we get too much information, especially we get the right information together with some information which is not correct. There are sometimes artefacts that are difficult to be interpreted.

Such as?

Such as mutations induced by PCR. PCR is a technique which can amplify millions of times DNA molecules.

You get complete artefact from PCR?

Yes but sometimes it generates artefacts and the next generation sequencing sees all these artefacts together with write mutations. So this is the reason we are cautious when we speak about the potential of this new technique.

That’s one potential limitation, are there others of this powerful new technique?

Other potential limitations, the difficulty is in the data analysis. Data analysis until now has been performed using specific tools that can be useful for scientific purposes but they cannot be used in clinics. These tools in clinics should be much easier and rapid. Technicians need rapid and easy things.

So the off the shelf reproducibility of the technique is an issue as well?

Yes, so these two are the main limitations of the techniques now – introducing errors and the difficulties of data management.

From the point of view of the cancer doctor with patients to treat, what are the successes that next generation sequencing has made so far?

Many because it has allowed us to detect new cancer genes that can become new targets for specific treatments. This is a very important thing. Another thing is that next generation sequencing is extremely powerful and sensitive so you can use this approach to detect genetic alterations in blood, not only in tumours but also in tumour cells in blood – circulating tumour cells or plasma or sera – and this is very important because tumours are heterogeneous and they give rise to metastasis. Metastases sometimes are different from the primary tumours and if you can look at the source and at the genes in the source in blood you are a further step.

And even free DNA in blood?

Yes, and free DNA too, yes. There are several studies dealing with the possibility to use next generation sequencing in circulating free DNA.

Now doctors tend to believe, and it is true in many categories of cancer, that the earlier you get the disease the better. Do you see a possible role for next generation sequencing in improving the detection rates of early cancer?

Yes, you’re right. An earlier detection is very important and we know by next generation sequencing that tumours become more complex during development. They start with just a few mutations and they become difficult to be treated because they accumulate mutations during redevelopment. So I think that next generation sequencing will be very important to follow the tumours during their development.

OK, so monitoring is important and you can change your therapy according to what you find, the molecular structures.

Tumour monitoring, yes. And also the detection of mutations in blood can allow you to easily monitor, could allow because now it’s not performed. But it could allow you in the near future to monitor the patient during treatment.

So you can see a role for sophisticated sequencing to tailor-make, individualise the therapy at each stage of the disease?

Yes, yes.

What about early detection, though, do you think you could reap a big harvest by giving people blood tests and saying, “Hey, you’ve got cancer,” and they wouldn’t have known otherwise?

Yes, of course the high sensitivity of next generation sequencing could allow us early detection and we have recently published a study dealing with the possibility to detect mutations in cells from bronchial lavages for instance. And this could be useful for early detection of tumours in non-small cell lung cancer.

So what are the take home messages, then, for doctors right now that they can possibly apply? Busy cancer doctors, what are the big things to remember about this which can hopefully be applied right away?

At the moment next generation sequencing is not ready to be used in clinical practice but we are very, very close to clinical application of next generation sequencing.

And do you see that coming quite soon?

Sure.

OK, well thank you very much Antonio.

Thank you.