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Pathologist Highlights Evolution of Genomic Testing in Cancer Care

Shannon Connelly
Published Online:1:00 PM, Mon May 27, 2019
Olga K. Weinberg, MD
Olga K. Weinberg, MD
Genomic testing, such as next-generation sequencing (NGS), has become increasingly more prevalent in oncology and is essential to patient care, explained Olga K. Weinberg, MD.

One of the ongoing challenges with reading the results of NGS, however, is determining which mutations are clinically relevant and which currently have no clinical significance. The role of NGS will continue to shift as more information is uncovered about the significance of different mutations, Weinberg said.

“What was [originally] felt to be not a real mutation, in the next few years as we learn more about that specific type of mutation, we may figure out that it was a real mutation and maybe it is clinically significant. As our landscape of understanding the results that we're getting back is changing, that also impacts our clinical practice,” said Weinberg.

In an interview with Targeted Oncology, Weinberg, director of hematopathology and flow cytometry, Department of Pathology, and assistant professor of pathology, Harvard Medical School, discussed how genomic testing has evolved over the years and how she envisions the role of NGS will change as more is learned about genetic mutations. 

Targeted Oncology: Can you discuss the importance of genomic testing?

Weinberg: In a setting of hematopoietic neoplasms, genetic testing is very important. It plays a role both in diagnosis and prognosis. It's especially important in acute leukemia where it helps us pick out patients who would do well or who may not do well, and therefore, targets therapy.

Targeted Oncology: What type of testing is typically ordered?

Weinberg: When we say genetic testing, there are different kinds of genetic testing. For a very long time, people were doing karyotype testing, which is still the gold standard. [That is] where you take a tissue like a bone marrow or a peripheral blood and you grow the cells and see if they have a normal number of cells and a normal number of chromosomes, or if they have loss of chromosomes or if they have moved around. That's a karyotype [test].

You can also do molecular testing where you look for mutations. Some of those could be acquired mutations or things you've had your whole life, or things that are associated with a neoplasm. Genetic testing is varied, and we do different types depending on the disease that we're working with.

Targeted Oncology: With molecular testing, are there any complications with regard to determining the difference between a fusion and a mutation?

Weinberg: Yes, you would generally need a different test to pick up a fusion versus a mutation. A mutation is a change at the molecular level, like a nuclear level, versus with a fusion you're taking parts of chromosomes and they're coming together in a particular way. 

Targeted Oncology: How can the results of genomic testing be used in prognosis and diagnosis?

Weinberg: There are some entities that are defined based on the abnormality that you see. For example, in a setting of acute myeloid leukemia, if you have translocations between chromosomes 15;17, that's defined as acute prolymphocytic leukemia. That has implications for therapies because there's a very specific therapy for that type of acute leukemia, but in other types of acute leukemias, if you have mutations like an MPN1mutation or a FLT3mutation, it helps to pick out patients that may respond well to induction or may need more intensive therapy like consolidation and transplant. 

Targeted Oncology: Now that there are many biomarkers that can lead treatment toward immunotherapy, is NGS becoming more prevalent?

Weinberg: NGS is probably more common in the world of myeloid neoplasms versus a lot of immunotherapy treatments now are more popular in the lymphoid world. But, NGS is definitely becoming a much more frequently used test that is applicable in both lymphoid and myeloid malignancies. 

Targeted Oncology: Are there challenges in terms of reading the results of a test?

Weinberg: Sometimes. Depending on where a test is obtained. For example, in an NGS test we may see mutations that are real versus mutations that are not significant, or they are what is called a “variant of unknown significance.” Different laboratories may not make a distinction between those 2 mutations, they may just list all the mutations they found and then it's up to the person reading that report to figure out whether those mutations are real or not. 

You can imagine that can be very challenging for a clinician that is very busy or a pathologist that is busy and the results may just get reported versus other laboratories might make a distinction. There is also an added challenge in that we learn more about these mutations as time goes on and we use NGS both in research and in the clinical setting. What was [originally] felt to be not a real mutation, in a few years as we learn more about that specific type of mutation, we may figure out that it was a real mutation and maybe it is clinically significant. As our landscape of understanding the results that we're getting back is changing, that also impacts our clinical practice.

Targeted Oncology: How do you see the use of genetic testing evolving going forward?

Weinberg: I think it's definitely here to stay. I think it's going to become even more prevalent. I think some of the struggles that we're facing with paying for some of these tests will have to be resolved because these tests are not going to go away, and I see these tests evolving into other maybe more specific tests as we figure out which mutations are important. Maybe we won't have such big panels, or maybe we'll have even bigger panels, or maybe the panels will be more specific for the types of diseases that the patients have. I think that these types of testing are central in patient care.

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