Paediatrics (RCH) - Research Publications

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Author: Desai, Jayesh × Author: Hansford, Jordan × Author: Ludlow, Louise × Start date: 2017 ×

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    Recurrent SPECC1L-NTRK fusions in pediatric sarcoma and brain tumors
    Khuong-Quang, D-A ; Brown, LM ; Wong, M ; Mayoh, C ; Sexton-Oates, A ; Kumar, A ; Pinese, M ; Nagabushan, S ; Lau, L ; Ludlow, LE ; Gifford, AJ ; Rodriguez, M ; Desai, J ; Fox, SB ; Haber, M ; Ziegler, DS ; Hansford, JR ; Marshall, GM ; Cowley, MJ ; Ekert, PG (COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2020-12)
    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.