JOURNAL ARTICLE

Recurrent SPECC1L-NTRK fusions in paediatric sarcoma and brain tumours

Dong-Anh Khuong-Quang, Lauren M Brown, Marie Wong, Chelsea Mayoh, Alexandra Sexton-Oates, Amit Kumar, Mark Pinese, Sumanth Nagabushan, Loretta Lau, Louise E Ludlow, Andrew J Gifford, Michael Rodriguez, Jayesh Desai, Stephen B Fox, Michelle Haber, David S Ziegler, Jordan R Hansford, Glenn M Marshall, Mark J Cowley, Paul G Ekert
Cold Spring Harbor Molecular Case Studies 2020 November 3
33144287
The identification of rearrangements driving expression of Neurotrophic Receptor Tyrosine Kinase (NTRK) family kinases in tumours has become critically important due to the availability of effective, specific inhibitor drugs. Whole genome sequencing (WGS) combined with RNA Sequencing (RNAseq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L-NTRK fusions identified in two paediatric central nervous system cancers and an extracranial solid tumour using WGS and RNAseq. These fusions arose either through a simple balanced rearrangement, or in the context of a complex chromoplexy event. We cloned the SPECC1L-NTRK2 fusion directly from a patient sample and showed that enforced expression of this fusion is sufficient to promote cytokine-independent survival and proliferation. Cells transformed by SPECC1L-NTRK2 expression are sensitive to a TRK inhibitor drug. We report here that SPECC1L-NTRK fusions can arise in a range of paediatric cancers. Whilst WGS and RNAseq are not required to detect NTRK fusions, these techniques may be of benefit when NTRK fusions are not suspected on clinical grounds or not identified by other methods.

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