Recurrent SPECC1L–NTRK fusions in pediatric sarcoma and brain tumors

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dc.contributor.authorKhuong-Quang, D.-A.
dc.contributor.authorBrown, L.M.
dc.contributor.authorWong, M.
dc.contributor.authorMayoh, C.
dc.contributor.authorSexton-Oates, A.
dc.contributor.authorKumar, A.
dc.contributor.authorPinese, M.
dc.contributor.authorNagabushan, S.
dc.contributor.authorLau, L.
dc.contributor.authorLudlow, L.E.
dc.contributor.authorGifford, A.J.
dc.contributor.authorRodriguez, M.
dc.contributor.authorDesai, J.
dc.contributor.authorFox, S.B.
dc.contributor.authorHaber, M.
dc.contributor.authorZiegler, D.S.
dc.contributor.authorHansford, J.R.
dc.contributor.authorMarshall, G.M.
dc.contributor.authorCowley, M.J.
dc.contributor.authorEkert, P.G.
dc.date.issued2020
dc.description.abstractThe 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.
dc.description.statementofresponsibilityDong-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, and Paul G. Ekert
dc.identifier.citationCold Spring Harbor Molecular Case Studies, 2020; 6(6):a005710-1-a005710-17
dc.identifier.doi10.1101/mcs.a005710
dc.identifier.issn2373-2873
dc.identifier.issn2373-2873
dc.identifier.orcidHansford, J.R. [0000-0001-7733-383X]
dc.identifier.urihttps://hdl.handle.net/2440/140338
dc.language.isoen
dc.publisherCold Spring Harbor Laboratory
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1079329
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1140626
dc.rights© 2020 Khuong-Quang et al. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.
dc.source.urihttps://doi.org/10.1101/mcs.a005710
dc.subjectBiomarkers, Tumor
dc.subjectBrain Neoplasms
dc.subjectCentral Nervous System Neoplasms
dc.subjectChild
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHumans
dc.subjectInfant
dc.subjectMembrane Glycoproteins
dc.subjectOncogene Proteins, Fusion
dc.subjectPhosphoproteins
dc.subjectProtein Kinase Inhibitors
dc.subjectReceptor, trkA
dc.subjectReceptor, trkB
dc.subjectSarcoma
dc.subjectWhole Genome Sequencing
dc.subject.meshHumans
dc.subject.meshSarcoma
dc.subject.meshCentral Nervous System Neoplasms
dc.subject.meshBrain Neoplasms
dc.subject.meshReceptor, trkA
dc.subject.meshReceptor, trkB
dc.subject.meshMembrane Glycoproteins
dc.subject.meshOncogene Proteins, Fusion
dc.subject.meshPhosphoproteins
dc.subject.meshProtein Kinase Inhibitors
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshChild
dc.subject.meshInfant
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshBiomarkers, Tumor
dc.subject.meshWhole Genome Sequencing
dc.titleRecurrent SPECC1L–NTRK fusions in pediatric sarcoma and brain tumors
dc.typeJournal article
pubs.publication-statusPublished

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