Molecular Testing to Treat and Diagnose Uterine Sarcoma


Matthew Ingham, MD, discusses understanding the genomics of sarcomas and how molecular testing can be useful in this space.

Matthew Ingham, MD, an assistant professor of Medicine in the Division of Hematology and Oncology at New York Presbyterian Hospital/Columbia University Medical Center, discusses understanding the genomics of sarcomas and how molecular testing can be useful in this space.

Uterine sarcoma is a rare disease with many different subtypes that are different both biologically and clinically. According to Ingham, experts must understand and treat these subtypes individually as they are all different.

Since these tumors can be genomically complex, Ingham discusses how molecular testing can be beneficial in this setting as it aids in diagnosing and treating patients.


0:08 | In sarcoma, I think we find that molecular testing really can help us in 2 ways. It can really help us from a diagnostic perspective. Some of the less common uterine sarcomas that I mentioned, like high-grade endometrial, stromal sarcoma, low- grade endometrial stromal sarcoma, do harbor some characteristic gene fusions that we would only pick up with molecular testing. Sometimes these diseases can be difficult to diagnose just based upon histology. I think the first use of molecular testing and sequencing is to help us make sure that we have the right diagnosis so we can offer the patient the best treatment.

0:42 | Then the second aspect of it is that sometimes genomics and understanding the molecular basis of the tumor will also help us with treatment selection. There's a couple of subtypes of uterine sarcoma where we actually find really actionable alterations. For example, PEComas are characterized by loss of this gene called tuberous sclerosis 2, TSC2. It is important to make that diagnosis because they can be very sensitive to target a class of drugs called mTOR inhibitors. There was just a drug that was approved that's very efficacious, and probably much more so than chemotherapy. Sometimes, we'll also find NTRK fusions, other highly actionable alterations, that can help us with targeted treatment.

1:25 | I think getting them more common uterine sarcoma, which is the uterine leiomyosarcoma, that's a subtype of sarcoma where we have some recurrent genomic alterations, oftentimes, we see p53 Rb deletions, those are the most common genomic events. Those are a little bit more challenging because we don't have a targeted drug that works directly against those alterations. What we're trying to do is understand the biological effects that some of those alterations have in uterine leiomyosarcoma if we can't target them directly. It seems that what they do is create a high level of replicative stress and related to that, we see that a lot of uterine leiomyosarcoma, they have homologous recombination deficiency. It does appear that it could be targetable with a novel class of drugs called PARP inhibitors, which I think is 1 of the most recent exciting advances in how we treat the most common type of uterine sarcoma, which is the uterine leiomyosarcoma.

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