Acquired PTEN Loss May Mediate Dabrafenib and Trametinib Resistance in BRAF V600E-Mutated Epithelioid Glioblastoma: A Case Report and Literature Review
Bibliographic record
Abstract
Epithelioid glioblastoma is a rare and aggressive variant of glioblastoma that is common in children and young adults. This variant frequently has a BRAF V600E mutation, and in recent years, this is often treated with BRAF and mitogen-activated protein kinase kinase inhibitors. An 18-year-old female initially presented with headaches and vomiting. They were diagnosed with an epithelioid glioblastoma and treated with temozolomide chemoradiotherapy. Upon progression, they had to redo surgery and then received dabrafenib and trametinib. They had one last surgery shortly before fatal tumour progression. Retrospective molecular analysis of three tumour specimens showed a PTEN mutation that arose upon first progression, but was not there initially. There were no new tumour mutations after initiation of dabrafenib and trametinib. The acquired PTEN mutation may have conferred resistance to dabrafenib and trametinib. This case highlights the potential importance of early treatment with BRAF and mitogen-activated protein kinase kinase inhibitors in high-grade BRAF V600E-mutated gliomas, ideally before the tumour develops resistance to targeted therapy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".