February 06, 2019
3 min read

Liquid biopsy may have 'amazing implications' for pediatric diffuse midline glioma

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Sabine Mueller, MD, PhD
Sabine Mueller

A test that identifies genetic mutations in the blood accurately detected a specific type of pediatric diffuse midline glioma that is associated with poorer clinical outcomes, according to study results.

“Now that we know it is possible to detect a genetic mutation associated with brain tumors in a noninvasive way, we think this approach could change how we follow patients in the clinic,” Sabine Mueller, MD, PhD, pediatric neuro-oncologist at UCSF Benioff Children’s Hospital San Francisco, said in a press release.

Mueller and colleagues assessed use of the liquid biopsy to detect major driver mutations associated with pediatric diffuse midline gliomas in a cohort of 48 patients, from whom they analyzed 110 specimens.

The test successfully detected the histone 3 p.K27M mutation — which is associated with a particularly aggressive form of the disease — in 88% of the cohort.

HemOnc Today spoke with Mueller about the novel test, the implications of the findings, and what still must be confirmed in research before it is ready for use in the clinic.

Question: How was this test developed?

Answer: The test was developed by my senior co-author, Javad Nazarian, PhD, scientific director of Children’s National Health System and George Washington University School of Medicine and Health Sciences, and his colleagues. They used patient plasma to isolate circulating tumor DNA and monitored for mutant gene copies that were shed by tumor cells. Using a sensitive method known as digital droplet PCR, Nazarian and colleagues identified genes found only in the plasma of patients with diffuse midline glioma. The test was developed further to mirror the current gold standard, MRI. The technology not only allows for a ‘yes’ or ‘no’ answer, but also for quantification, providing a sensitive and complementary technology to aid MRI and other clinical assessments of tumor growth and response.

Q: What type of correlations have been observed so far?

A: For some patients, after they had radiation therapy and the tumor responded, we saw a decline in the amount of circulating tumor DNA. In some patients, we also observed a subsequent increase of circulating tumor DNA that corresponded to progression based on imaging, as well as clinical findings.

Q: What still needs to be confirmed in research?

A: This is still a research test and there are still things that need to be ironed out. At the current time, I would not base any clinical decisions on the findings of this study, but we are getting closer to hopefully implementing the test in the clinic.


Q: What are the potential implications if this test is proven safe and effective?

A: It could have amazing implications, because this test could help with diagnosis. For the longest time, the neuro-oncology community was not comfortable to biopsy these tumors because of the location of the tumor and the expected risk for the patient. In addition, the results would have little impact on the therapy decisions. As more centers decided to biopsy these cases routinely, we learned that this can be done relatively safely and most patients do very well after a biopsy. However, it remains an invasive and risky procedure. If we could have a marker that we could identify in the blood, then this could have a huge impact on diagnosis.

Further, if we could expand the platform to look at multiple mutations, then we could follow these tumors in a noninvasive manner more closely to identify potential changes that occur with therapy and understand better why the therapy is failing. This is a critical step to improve our current approaches.

As we are starting to use immunotherapy in these children, imaging is harder to interpret because these patients can develop an initial inflammatory response that may present as tumor growth on imaging when, in fact, the tumor is responding. We often refer to this as pseudoprogression. In these cases, therapy is sometimes aborted too early. A more quantitative marker, such as liquid biopsy, has the potential to help identify these cases more accurately. – by Jennifer Southall


Panditharatna E, et al. Clin Cancer Res. 2018;doi:10.1158/1078-0432.CCR-18-1345.

For more information:

Sabine Mueller, MD, PhD, can be reached at the UCSF Benioff Children’s Hospital, 550 16th St., 4th Floor, San Francisco, CA 94143; email: sabine.mueller@ucsf.edu.

Disclosure: Mueller reports no relevant financial disclosures.