Evidence map›Paper›PMID 40348911›Full record

ArticleNPJ precision oncology2025

A novel TRKB-activating internal tandem duplication characterizes a new mechanism of receptor tyrosine kinase activation.

Lauren M Brown, Gabor Tax, Pablo Acera Mateos, Antoine de Weck, Steve Foresto, Thomas Robertson, Fatimah Jalud, Pamela Ajuyah, Paulette Barahona, Jie Mao and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Lauren M BrownChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Gabor TaxChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Pablo Acera MateosChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Antoine de WeckChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Steve ForestoQueensland Children's Hospital, Brisbane, QLD, Australia.
Thomas RobertsonQueensland Children's Hospital, Brisbane, QLD, Australia.
Fatimah JaludPeter MacCallum Cancer Centre, Parkville, VIC, Australia.
Pamela AjuyahChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Paulette BarahonaChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Jie MaoChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
M Emmy M DolmanChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Marie WongChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Chelsea MayohChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Mark J CowleyChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Loretta M S LauChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.
Teresa SadrasPeter MacCallum Cancer Centre, Parkville, VIC, Australia.
Paul G EkertChildren's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia. pekert@ccia.org.au.

Funding

National Health and Medical Research Council 2028235The Kids Cancer Project Col Reynolds Mid-Career Fellowship
6 · The paper itself

Abstract

Precision medicine programs like the Zero Childhood Cancer Program perform comprehensive molecular analysis of patient tumors, enabling detection of novel structural variants that may be cryptic to standard techniques. Identification of these variants can impact individual patient treatment, and beyond this establish new mechanisms of oncogenic activation. We have identified a novel internal tandem duplication (ITD) in the receptor tyrosine kinase (RTK), NTRK2, in a patient with FOXR2-activated CNS neuroblastoma. The ITD spans exons 10-13 of NTRK2 encoding the transmembrane domain. NTRK2 ITD is transforming and sensitive to TRK inhibition. In silico structural predictions suggested the duplication of an alpha-helix region and juxtaposed tyrosine residues that play a role in facilitating autophosphorylation. Consistent with this, mutation of these residues inhibited cellular transformation. This is the first report of an ITD spanning the transmembrane domain of an RTK, characterizing an additional mechanism by which RTKs are activated in cancer.

Identifiers

PMID40348911
PMCPMC12065843

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.