Advances in Genetic Testing for Patients With Gastrointestinal Cancers

Michael Hall, MD, Fox Chase Cancer Center, Philadelphia, Pennsylvania, reviews his presentation from the 2022 Great Debates & Updates in Gastrointestinal Malignancies virtual meeting, on the changes and advances that have occurred in the field of genetic testing for gastrointestinal cancers.

Transcript:

My name is Dr. Michael Hall. I'm a professor at Fox Chase Cancer Center in Philadelphia, Pennsylvania. I'm the Chair of the Department of Clinical Genetics. At the upcoming Great Debates & Updates in Gastrointestinal Malignancies meeting, I will be discussing some of the changes and the advances that we're seeing in the field of gastrointestinal genetic testing and risk assessment.

The first topic I'll cover is how patients are coming to us in the risk assessment clinic. This is changing a lot over the years, so I'll be talking about what is changing for how patients are identified. What's changing in terms of how we interpret and manage genetic testing results? What's changed in terms of the kinds of patients who are coming to us and their diagnoses? And finally, what's important for us to understand about changes in the indeterminate testing rates for patients who do undergo genetic testing?

Then I'm going to move on to talk a little bit about the conduct of testing, and again, how that has evolved over the years. I'm going to compare and contrast how testing was conducted basically through about 2015 before next generational sequencing came along, and then how we've been performing things since panel-based testing has become available. I'll talk a little bit about the pros and cons of panel-based testing, how it has impacted counseling and management recommendations.

I'll also talk about three areas, including something known as pleiotropy, genetic heterogeneity, and the variable penetrance of genes, and how all of these various aspects of hereditary risk genetics have been somewhat improved by the introduction of panel-based testing. And so why panel-based testing has, in many ways improved our ability to identify mutation carriers in the population.

From there, I'm going to move on to where is risk assessment and genetic testing most relevant in GI cancers? I'm going to split the group of patients who are eligible for GI genetic testing into a high relevance, sometimes relevant, and then a less relevant group. And I'll talk about which genes are involved in each of those groups and diagnoses to kind of separate this down and make it easier for docs who are out practicing to understand when they should be thinking more about risk assessment and genetic testing for GI cancers, and when they can forego that and focus more on treatment.

From there, I'll go on to some of the basic criteria that can help docs identify patients for risk assessments such as early onset disease, multiple cancers, bilateral cancers, and some of the specific pathologies and findings in patients such as diffuse gastric cancer, skin findings, and lynch syndrome or extra-colonic findings of FAP.

As I'm heading to a close, I'll talk a little bit about eligible patients who have presentations that can be a little trickier and can fool us, just so those are on the radar of docs that some of the other criteria I mentioned don't always cover these patients. I call them the 4 zebras: recessive genes, de novo mutations, founder mutations, and patients with multiple mutations that need to be found.

Finally, I'll talk about a couple of the newer changes that have happened in GI genetic testing in the last few years, including testing all pancreatic cancers and a recent move on and changes in the NCCN guidelines about potentially changing early onset colon cancer testing to pan testing of all colon cancers similar to pancreas cancer.

Finally, I'll wrap up by reviewing some of the major syndromes that we see in GI genetics including lynch syndrome, FAP-MUTYH, hereditary pancreatic cancer and hereditary gastric cancer, and then finally colorectal cancer polyposis, as these are kind of the core areas that every doc probably should be familiar with when they are thinking about which patients need to be tested in the clinic.

So that will be my talk. I'm going to get that all done hopefully in 20 minutes, and I'm very grateful for the invitation to give this presentation. Thank you.

Source:

Hall M. Genetic Testing for GI Cancers. Presented at Great Debates & Updates in Gastrointestinal Malignancies; November 16-18, 2022; virtual.