KGHRI researcher co-leads study of improved cancer screening technique

KGHRI molecular geneticist and Queen’s University cancer researcher Harriet Feilotter (Pathology and Molecular Medicine) is co-leading a multi-institutional study with Dr. John Bartlett of the Ontario Institute for Cancer Research (OICR) on the efficacy of a genetic sequencing assay that tests more than 100 genetic mutations in cancer cells. (An assay is a molecular test that looks for biomarkers for diagnosing disease or predicting response to drugs.)

This test could accelerate personalized patient care by linking these mutations to new treatment options.

“Many gene mutations we know influence the behaviour of tumors,” Dr. Feilotter explains. “For example in lung cancer, the presence of a certain gene mutation may show whether a patient will respond to a therapy – or not.”

The study will use a next-generation comprehensive sequencing assay produced by partner group Thermo Fisher. KGH was one of the first hospitals in Ontario to have next-generation sequencing platform, a leading-edge technology that can analyze many genes simultaneously, rather than one gene at a time. “Analyzing DNA of tumors isn’t new, but to do it in this large scale way on such small amounts of tissue sample, that’s very new,” she says.

“From my own research on the assay, I had already decided that it should be brought to Ontario clinical labs, but I didn’t have a mechanism for doing that due to financial restraints,” says Dr. Feilotter. “This collaboration with Dr. Bartlett at the OICR and Thermo Fisher presents a fortunate opportunity to put the assay through its paces, show its effectiveness and give clinicians a new diagnostic tool to use in plotting a course of treatment against cancer.”

Rather than testing for mutations individually, the assay tests for mutations or changes to more than 100 genes commonly associated with different types of cancer. Unlike many currently used panels, which can only measure one type of mutation at a time, the assay can simultaneously test many mutations of multiple types from the same small tissue sample. This allows not only for more information to be collected from less tumor material, but also allows clinicians the opportunity to produce a “big picture” view of the mutation spectrum present in each particular tumor. Physicians would also be able to prescribe treatment plans that target the specific mutations present in the tumor, leading to more targeted cancer treatments.

In phase one of this study, researchers at both Queen’s University and OICR/Sunnybrook Health Sciences Centre will test the same breast cancer samples to establish whether results are reproducible at different sites. The OICR will provide the tissue samples, all of which will have been previously analyzed so the assay’s effectiveness can be measured against a known value. The second phase of the study will use a more complex design that examines more than 200 genes, to again demonstrate replicability.

“Thermo Fisher has been very engaged in making sure the assay is robust,” says Dr. Feilotter. “You don’t want to miss a mutation and you don’t want to call one when it’s not there because the downstream effect of such an error is that your patient does or doesn’t get a drug.”

In the final phase of the study, five additional Ontario clinical labs will be included, and will start using the assay on a common set of tumor samples. Dr. Feilotter says the findings of that study will be used to assess the technology for use in the clinic. The assay would need to be shown to produce accurate results in a clinical setting – without the need for regular adjustments as one might find in a research laboratory.

“The difference between a research lab and a clinical lab is that the clinical setting, you need to be able to run the assay the same way for every sample,” she explains. “We want to know how the assay performs when it has to stick to one setting. If we can then show that, across the province, the test is robust and works well, we’ll be in a position ask the Cancer Care Ontario and the Ministry of Health to look at supporting this assay for particular types of tumors.”