State-of-the-art molecular diagnostics for brain tumor care

March 24, 2023

Molecular diagnostics plays an increasingly important role in managing brain tumors. As part of Mayo Clinic's multidisciplinary neuro-oncology team, neuropathologists and geneticists facilitate individualized tumor treatment.

"We provide extra information that helps refine the final diagnosis," says Robert B. Jenkins, M.D., Ph.D., a medical geneticist and pathologist in the Mayo Clinic Comprehensive Cancer Center at Mayo Clinic in Rochester, Minnesota. "Our current database has molecular information on more than 20,000 patients. Accessing that extensive experience is a tremendous resource."

Laboratory Genetics and Genomics at Mayo Clinic tests more than 1,500 brain tumors a year. Test samples are first accessioned by Mayo Clinic Laboratories — one of the largest reference labs in the United States — before being sent to a specialty area such as cytogenetics, molecular genetics or genomics sequencing.

"Because our practice is distributed across all of these disciplines, we see different kinds of tumors, including many rare tumors," Dr. Jenkins says.

An integrated approach

In recent years, neuropathologists have uncovered new tumors with similar histologic features or patterns of genetic alterations. The World Health Organization (WHO) incorporated many of these molecular diagnostics discoveries in its updated classification of central nervous system tumors, which was issued in 2021.

Mayo Clinic takes an integrated approach to molecular diagnostics. Neuropathologists provide an initial assessment of an individual's tumor sample. Based on that assessment, specific genetic tests are ordered.

Comprehensive genetic tests include:

A neuro-oncology next-generation sequencing panel, which identifies mutations, gene fusions and transcript variants associated with brain tumors.
A chromosomal microarray, which evaluates copy number changes in brain tumor samples.

A multidisciplinary team discusses test results.

"Our integrated approach is what makes us unique."

— Cristiane (Cris) M. Ida, M.D., a molecular neuropathologist at Mayo Clinic's campus in Minnesota

"The pathologists share what they are seeing and look at the genetic testing results," she says. "Then, we use WHO's 2021 classification system to diagnose each brain tumor case. We put the cases into different 'buckets' that are highly associated with specific clinical outcomes over time."

Mayo Clinic's clinician-researchers also are discovering new genetic alterations that affect brain tumor diagnosis and prognosis.

As described in the October 2022 issue of Science, researchers co-led by Dr. Jenkins found that a specific germline alteration — known as rs55705857 — confers a greatly increased risk of IDH-mutant low-grade glioma. The finding might eventually lead to new therapies targeting that DNA alteration.

"Every day, we are determining how patients will be managed, because the management depends upon the pathologic diagnosis and upon the genetic results," Dr. Jenkins says. "In short, our work always puts the needs of the patient first."