Brain Tumours
Central nervous system tumour classification is now explicitly integrated: molecular features sit alongside histology in defining the diagnosis itself. Two tumours that look similar under the microscope may be different diseases if their molecular profiles differ.
Disease categories
Major disease categories
- Glioblastoma
- IDH-mutant astrocytoma
- Oligodendroglioma
- Meningioma
- Ependymoma
- Medulloblastoma
- CNS lymphoma
- Brain metastases
Molecular
Molecular considerations
IDH1 and IDH2 status, 1p/19q co-deletion, MGMT promoter methylation, ATRX and TERT promoter status, and EGFR amplification are among the features integral to classification and discussion. Medulloblastoma is divided into molecular subgroups with distinct behaviour.
Markers commonly discussed in brain tumours
- IDH1 / IDH2
- 1p/19q co-deletion
- MGMT promoter methylation
- ATRX
- TERT promoter
- EGFR amplification
- H3 K27M
- BRAF V600E
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
Integrated histological and molecular diagnosis is standard practice. DNA methylation profiling is increasingly discussed for difficult cases.
Germline
Germline considerations
Considered where a syndromic pattern is present — for example Li-Fraumeni, neurofibromatosis or Turcot syndrome.
Molecular monitoring
ctDNA and liquid biopsy considerations
Plasma ctDNA is limited by the blood–brain barrier. Cerebrospinal fluid analysis is an area of active research.
Single-cell & computation
Single-cell and algorithmic approaches
Single-cell sequencing in glioma has described a cellular hierarchy in which stem-like populations persist through treatment and are implicated in recurrence — a structure invisible to bulk profiling, which reports their average. Single-cell DNA analysis addresses the pronounced regional heterogeneity of these tumours, where a single biopsy may not represent the lesion. The dominant algorithmic contribution in neuro-oncology has been DNA methylation classification, which resolves diagnostically difficult cases more reliably than histology alone and is now a routine part of the discussion in hard cases. Related work covers cerebrospinal fluid analysis methods, given how poorly plasma ctDNA performs across the blood–brain barrier.
In practice
What a review of this disease typically surfaces
The recurring issue is a diagnosis made on histology alone, without the molecular markers the current classification requires. Two tumours that look alike under the microscope may be different diseases. MGMT promoter methylation status is often missing. Where imaging has changed after treatment, pseudoprogression and true progression have frequently not been distinguished, and cases are sometimes reclassified as progressive on that basis alone.
Patterns observed across precision oncology case reviews. Every case differs; these are the questions worth checking, not conclusions about any individual patient.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is the diagnosis integrated, combining histology with the required molecular markers?
- Has MGMT promoter methylation been assessed where relevant?
- Has methylation profiling been considered for a difficult diagnosis?
Resistance
Resistance and recurrence questions
- Has pseudoprogression been distinguished from true progression?
- Has re-biopsy been considered where the diagnosis is in doubt?
Trials
Clinical trial considerations
Molecular classification is frequently determinative for eligibility in neuro-oncology trials.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.