The impact of next gen sequencing and whole genome sequencing in the molecular diagnostics of cancer patients

In order to map the human genome, in which the complete genetic composition of man can be found, there are promising techniques such as next gen sequencing and whole genome sequencing. Ed Schuuring, Professor of Molecular Oncological Pathology and Clinical Molecular Biologist in Pathology at the UMCG, talks about a number of these developments.

By: Dimitri Reijerman

Schuuring and his colleagues are researching cancer cells, among other things. He says:
“When we receive a tumor biopsy, a piece of human tissue, in pathology, we have been looking for certain characteristics for a hundred years – ever since the microscope was invented – to see if it is cancer and if so, what type of cancer. In recent years, the field has improved greatly by, for example, looking at protein expressions that contribute to the staging and better classification of tumors. The new development is that we can now characterize tumors even better and provide more optimal treatments based on the genetic composition of a tumor.”

“You see that everything is slowly shifting towards molecular diagnostics, towards research methods that allow you to create a genetic tumor profile using next-gen sequencing, for example. I expect that pathologists will soon need the microscope much less often than we do at present.”

 “An important new development in the treatment of cancer patients is that for some genetic abnormalities found in the tumor, specific drugs are available that target the cancer cells with this abnormality,” says the professor. “We have a list of about fifteen to thirty markers for which we have a targeted drug available. We call this customized therapy. The treatment of lung cancer is the most advanced in this respect. The official national guideline for lung cancer already mentions 12 genes that must be tested and for which, if an abnormality is found, targeted therapy is available. The drug in question must be included in the basic package, be regulated and easily available to all patients.

More expensive but more efficient

Schuuring explains further: “Developments are not standing still and more and more new drugs targeting abnormalities in yet other genes are becoming available that are effective in clinical studies. Although the costs for these tests are currently not fully reimbursed, we should also test for these genes in order to make the new targeted drugs accessible to all cancer patients. So as a patient, you would already want to be tested for a broad package of genes. I think that we should ultimately look at at least fifty genes. This would lead to a broad next-gen sequencing method, in which you do not look at one genetic abnormality but at many abnormalities at the same time. In fact, this would make a significant efficiency gain: the NGS test is somewhat more expensive than a single-gene test, but you do look at dozens of genes at the same time.”

And finally, there is whole genome sequencing (WGS): “These tests are relatively expensive, but they do map the entire genome (i.e. all genetic abnormalities) of a tumor. That is the shift, driven by all the new medicines that are coming. The use of WGS has several consequences, says Schuuring: “Suppose you sequence the entire genome with WGS for lung cancer. This can reveal many different DNA abnormalities. But if you can't do anything with most of the information, then that is an important reason to not only use WGS but also broad NGS with which you can analyze more than 500 genes. An important consideration for using broad NGS tests is that these tests are not only used on fresh/frozen tissue but also on embedded tissue (in paraffin blocks) that is stored as standard from all tissue in all pathology labs, and that broad NGS can currently identify all relevant DNA abnormalities. “That is why I do not expect widespread use of expensive WGS in current diagnostics in the coming years, except for very specific diagnostic questions such as in pediatric oncology or in cases of unknown primary tumor.”

“There is also a political side to it: how do these developments fit into current healthcare? I help advise the minister on how we can better organize healthcare over the next five years and offer every cancer patient in the Netherlands equal opportunities for access to all available targeted medicines. It is a completely different diagnostics than what we do now. It costs a lot of money and in the current setting we should start cutting back on healthcare sooner.”