BRAF fusion or rearrangement

aka BRAF fusion, KIAA1549-BRAF, KIAA1549::BRAF, BRAF rearrangement, BRAF-fused glioma

A BRAF fusion joins another gene to the BRAF kinase, most often KIAA1549 in paediatric low-grade glioma. Tovorafenib is approved for children whose relapsed low-grade glioma carries a BRAF fusion or V600 mutation.

KIAA1549::BRAF is the hallmark of pilocytic astrocytoma and most paediatric low-grade gliomas; other partners and rare BRAF fusions occur in melanoma, thyroid and pancreatic acinar cancers. Fusions behave as class II alterations and respond poorly to first-generation BRAF inhibitors, which can paradoxically activate them. Tovorafenib (Ojemda, 2024) is labelled for patients 6 months and older with relapsed or refractory paediatric low-grade glioma harbouring a BRAF fusion or rearrangement or a BRAF V600 mutation; FoundationOne CDx is the listed companion diagnostic (P170019/S054). Detection needs RNA or DNA sequencing that captures rearrangements, or FISH; hotspot PCR misses them.

Part ofBRAF· BRAFOther readoutsBRAF class II and class III mutations BRAF V600E All readouts

BRAF: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · BRAF is a signalling kinase mutated in half of melanomas; blocking it with two drugs at once became a template for targeted therapy.

Sequencing 1 approval threshold

What it means for a patient

In a child's low-grade glioma a BRAF fusion is common and, if the tumour comes back after treatment, makes tovorafenib an on-label option taken by mouth. The first-generation BRAF tablets used for V600E melanoma are not suitable for fusions. Ask whether the test used could see rearrangements, because some panels cannot.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

A BRAF gene fusion or rearrangement (for example KIAA1549::BRAF) detected by RNA or DNA sequencing or FISH; hotspot PCR does not detect it.

“BRAF V600 mutations and BRAF fusions”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
BRAF fusion or rearrangement, or BRAF V600 mutation	Tovorafenib	Paediatric low-grade glioma	FDA	label

Drugs whose label names it

Tovorafenib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
FoundationOne CDx	Foundation Medicine	Low-Grade Glioma - Tissue	Tovorafenib	P170019/S054 (01/16/2025)

Tests that measure it

FoundationOne CDx Tempus xT and xT CDx FoundationOne CDx Caris MI Profile Illumina TruSight Oncology Comprehensive

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.