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Khuong-Quang, Dong-Anh; Brown, Lauren M; Wong, Marie; Mayoh, Chelsea; Sexton-Oates, Alexandra; Kumar, Amit; Pinese, Mark; Nagabushan, Sumanth; Lau, Loretta; Ludlow, Louise E; Gifford, Andrew J; Rodriguez, Michael; Desai, Jayesh; Fox, Stephen B; Haber, Michelle; Ziegler, David S; Hansford, Jordan R; Marshall, Glenn M; Cowley, Mark J; Ekert, Paul G
Cold Spring Harbor molecular case studies, 12/2020, Letnik: 6, Številka: 6Journal Article
The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase ( ) 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 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 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 expression are sensitive to a TRK inhibitor drug. We report here that fusions can arise in a range of pediatric cancers. Although WGS and RNA-seq are not required to detect fusions, these techniques may be of benefit when fusions are not suspected on clinical grounds or not identified by other methods.
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in: SICRIS
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