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Recurrent SPECC1L-NTRK fusions in pediatric sarcoma and brain tumors.


ABSTRACT: The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase (NTRK) family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L-NTRK fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor using WGS and RNA-seq. 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 pediatric cancers. Although WGS and RNA-seq 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.

SUBMITTER: Khuong-Quang DA 

PROVIDER: S-EPMC7784491 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase (<i>NTRK</i>) family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three <i>SPECC1L-NTRK</i> fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor u  ...[more]

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