Why are brain tumors hard to classify?
Around 100 types of tumor of the central nervous system, meaning the brain and spinal cord, are known. Some can often be cured by surgery alone, others are very aggressive. Getting the tumor type right therefore guides the whole treatment.
Diagnosis relies on a neuropathologist examining tissue under the microscope. Yet for many tumor types, two doctors looking at the same sample do not always reach the same conclusion.
The researchers looked for a more objective signature, written in the tumor's own DNA.
What did the researchers do?
They focused on DNA methylation: small chemical marks on DNA that control which genes are switched on. Each tumor type keeps its own pattern of marks, a bit like a fingerprint.
The team gathered 2,801 reference samples across 91 classes, including healthy brain tissue. A machine learning tool, a random forest of 10,000 decision trees, learned to recognize each class. It gives a confidence score: above 0.9, the tumor is matched to a class.
The tool was then tested in real conditions on 1,155 new cases, before being offered free online.
What were the results?
A methylation profile could be made for 1,104 tumors. The tool matched 88% of them to a known class with a score of at least 0.9. For 76% of the tumors analyzed, its result agreed with the diagnosis under the microscope.
In 139 cases, the two results differed. After further tests, the original diagnosis was revised in 129 of those cases, in favor of the class suggested by the tool. That is 12% of all cases.
In 171 cases, the tool also identified a molecular subgroup that the microscope alone could not reveal.
Key figures
- 2,801reference samples across 91 classes
- 88%of profiled tumors matched to a class with a score of at least 0.9
- 12%of cases whose diagnosis was revised thanks to the tool
Facing a brain tumor: keeping your questions close
This tool is already used in some specialist centers, alongside the microscope. So the diagnosis of a brain tumor may rely on several tests, which can take time.
Mima helps you keep track of your reports, your appointments and what worries you between visits, for yourself or someone close. A useful question for the neuro-oncologist: "Has a molecular test of the tumor, such as methylation profiling, been done?"
What does this mean for patients?
A more precise diagnosis can change the treatment offered and the information given about how the disease may develop. The tool is free online and needs no computer analysis on site, which opens it up to many hospitals.
It does not replace the neuropathologist: it adds to the microscope for a diagnosis that combines how the tissue looks with its molecular profile.
What are the limits?
In 4% of cases the sample was not suitable, often because it held too few tumor cells. And not every profiled tumor could be matched to a class with enough confidence.
The authors note that the cases studied did not exactly reflect everyday practice. The tool also depends on the equipment needed to measure DNA methylation, which is not available everywhere.
Frequently asked questions
What is DNA methylation?
Small chemical marks on DNA that control which genes are switched on. Each tumor type has its own pattern of marks, which helps identify it.
Does this tool replace the doctor?
No. It adds to the neuropathologist's microscope examination. The final diagnosis combines both.
Is the tool used in hospitals?
In the study it was applied in routine diagnosis and made freely available online. But it needs equipment to measure methylation, which not every hospital has.
How many diagnoses changed?
In the study, the original diagnosis was revised in 129 cases, or 12% of the cases tested in routine care.
The original study
Capper D, Jones DTW, Sill M, et al. “DNA methylation-based classification of central nervous system tumours.” Nature, March 14, 2018. DOI : 10.1038/nature26000
Read the full study in NatureThis article summarizes a scientific study and is not medical advice.