biomarkersBiomarker

RET fusion and RET mutation

aka RET fusion, RET rearrangement, RET fusion-positive, KIF5B-RET, KIF5B::RET, CCDC6-RET, RET mutation, RET M918T, RET-mutant medullary thyroid cancer, RET-altered

RET fusions drive 1 to 2 percent of lung cancers and some thyroid cancers; RET point mutations drive medullary thyroid cancer. Selpercatinib is approved for RET fusions in any solid tumour and for RET-mutant medullary thyroid cancer; pralsetinib for RET fusion lung cancer.

RET fusions (KIF5B::RET, CCDC6::RET, NCOA4::RET) are detected by RNA or DNA sequencing and FISH; RET point mutations (M918T, codon 634 and others, germline in MEN2) by sequencing. Selpercatinib (Retevmo) is labelled for RET fusion-positive NSCLC, RET fusion-positive thyroid cancer, RET-mutant medullary thyroid cancer and, since 2022, RET fusion-positive solid tumours after prior therapy, each as detected by an FDA-approved test; pralsetinib (Gavreto) for RET fusion-positive NSCLC. The Oncomine Dx Target Test, FoundationOne CDx and TruSight Oncology Comprehensive are the listed companion diagnostics.

Part ofRET· RET All readouts

RET: 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 · RET is a kinase altered in thyroid cancer and a small slice of lung cancer, treatable with one selective pill regardless of where the tumour is.

Sequencing 3 approval thresholds

What it means for a patient

A RET fusion means selpercatinib (or, in lung cancer, pralsetinib) is an on-label tablet whatever the cancer type once other treatment has been tried, and first line in lung cancer. In medullary thyroid cancer a RET point mutation qualifies for selpercatinib too, and if the mutation is inherited (MEN2) relatives should be tested.

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 RET gene fusion by RNA or DNA sequencing (or FISH), or an activating RET point mutation, small deletion or insertion by sequencing.

“RET fusions; RET mutations (SNVs, MNVs, and deletions)”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
RET fusion-positive	Pralsetinib	Non-small-cell lung cancer	FDA	label
RET fusion-positive (NSCLC, thyroid, solid tumours) and RET-mutant medullary thyroid cancer Retevmo label indications 1.1 to 1.4 (DailyMed set id 7fa848ba): RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer, RET fusion-positive thyroid cancer, and RET fusion-positive solid tumours after prior systemic treatment, each as detected by an FDA-approved test.	Selpercatinib	Medullary thyroid cancer	FDA	label
RET fusion-positive FDA companion diagnostic rows for the Oncomine Dx Target Test (P160045/S031) and TruSight Oncology Comprehensive (P230011) with Retevmo in NSCLC.	Selpercatinib	Non-small-cell lung cancer	FDA	label

Drugs whose label names it

Pralsetinib Selpercatinib

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
Oncomine Dx Target Test	Life Technologies (Thermo Fisher Scientific)	Non-Small Cell Lung Cancer (NSCLC) - Tissue	Pralsetinib	P160045/S019 (09/04/2020)
Oncomine Dx Target Test	Life Technologies (Thermo Fisher Scientific)	Medullary Thyroid Cancer (MTC) - Tissue	Selpercatinib	P160045/S031 (09/21/2022)
FoundationOne CDx	Foundation Medicine	Solid Tumors - Tissue	Selpercatinib	P170019/S043 (10/06/2023)
TruSight Oncology Comprehensive	Illumina	Non-Small Cell Lung Cancer (NSCLC) - Tissue	Selpercatinib	P230011 (08/21/2024)

Tests that measure it

FoundationOne CDx Oncomine Dx Target Test Tempus xT and xT CDx FoundationOne CDx Caris MI Cancer Seek Guardant360 CDx 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.