Fusion genes with<i>ALK</i>as recurrent partner in ependymoma-like gliomas: a new brain tumor entity?

Olsen, Thale Kristin; Panagopoulos, Ioannis; Meling, Torstein R.; Micci, Francesca; Gorunova, Ludmila; Thorsen, Jim; Due-Tønnessen, Bernt Johan; Scheie, David; Lund‐Iversen, Marius; Krossnes, Bård Kronen; Saxhaug, Cathrine; Heim, Sverre; Brandal, Petter

doi:10.1093/neuonc/nov039

Cited by 47 publications

(47 citation statements)

References 51 publications

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“…ALK fusions are well‐known therapeutic targets detected in various types of cancer . In the present case, as observed in other recurrent ALK fusions, the kinase domain of ALK and the coiled‐coil domain of its fusion partner, PRRC2B , were retained .…”

supporting

confidence: 71%

Subependymal giant cell astrocytoma harboring a PRRC2B‐ALK fusion: A case report

Tsurubuchi

Nakano²,

Hirato

et al. 2019

Pediatric Blood & Cancer

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supporting

confidence: 71%

Subependymal giant cell astrocytoma harboring a PRRC2B‐ALK fusion: A case report

Tsurubuchi

Nakano²,

Hirato

et al. 2019

Pediatric Blood & Cancer

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“…She underwent GTR alone and has been disease free for over 8 years. Anaplastic lymphoma kinase (ALK) gene fusions have been observed in numerous pediatric cancers, including CNS tumors . PPP1CB‐ALK fusion has only been reported in one case of congenital HGG; the patient did well following resection alone .…”

Section: Resultsmentioning

confidence: 67%

“…ALK gene fusions were first identified in anaplastic large‐cell lymphoma but now have been reported in many different pediatric cancers . Olsen et al described ALK fusions in ependymoma‐like gliomas, including KTN1‐ALK and CCDC88A‐ALK . Fusions involving PPP1CB are less common and have most frequently been reported in leukemias (fused with YPEL5) and recently reported as PPP1CB‐ALK in a patient with uterine leiomyosarcoma .…”

Section: Novel and Rare Fusion Events In Pediatric Gliomasmentioning

confidence: 99%

Targeted fusion analysis can aid in the classification and treatment of pediatric glioma, ependymoma, and glioneuronal tumors

Lake

Donson

Prince

et al. 2019

Pediatric Blood & Cancer

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Background The use of next‐generation sequencing for fusion identification is being increasingly applied and aids our understanding of tumor biology. Some fusions are responsive to approved targeted agents, while others have future potential for therapeutic targeting. Although some pediatric central nervous system tumors may be cured with surgery alone, many require adjuvant therapy associated with acute and long‐term toxicities. Identification of targetable fusions can shift the treatment paradigm toward earlier integration of molecularly targeted agents. Methods Patients diagnosed with glial, glioneuronal, and ependymal tumors between 2002 and 2019 were retrospectively reviewed for fusion testing. Testing was done primarily using the ArcherDx FusionPlex Solid Tumor panel, which assesses fusions in 53 genes. In contrast to many previously published series chronicling fusions in pediatric patients, we compared histological features and the tumor classification subtype with the specific fusion identified. Results We report 24 cases of glial, glioneuronal, or ependymal tumors from pediatric patients with identified fusions. With the exception of BRAF:KIAA1549 and pilocytic/pilomyxoid astrocytoma morphology, and possibly QKI‐MYB and angiocentric glioma, there was not a strong correlation between histological features/tumor subtype and the specific fusion. We report the unusual fusions of PPP1CB‐ALK, CIC‐LEUTX, FGFR2‐KIAA159, and MN1‐CXXC5 and detail their morphological features. Conclusions Fusion testing proved to be informative in a high percentage of cases. A large majority of fusion events in pediatric glial, glioneuronal, and ependymal tumors can be identified by relatively small gene panels.

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“…DNA was extracted from frozen tumor tissue (Olsen et al, 2014) and RNA extraction and pairedend high-throughput sequencing (Olsen et al, 2015) was performed as previously described.…”

Section: Dna and Rna Extraction High-throughput Sequencing And Bioimentioning

confidence: 99%

Novel fusion genes and chimeric transcripts in ependymal tumors

Olsen

Panagopoulos

Gorunova

et al. 2016

Genes Chromosomes & Cancer

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We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc.

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Fusion genes withALKas recurrent partner in ependymoma-like gliomas: a new brain tumor entity?

Cited by 47 publications

References 51 publications

Subependymal giant cell astrocytoma harboring a PRRC2B‐ALK fusion: A case report

Subependymal giant cell astrocytoma harboring a PRRC2B‐ALK fusion: A case report

Targeted fusion analysis can aid in the classification and treatment of pediatric glioma, ependymoma, and glioneuronal tumors

Novel fusion genes and chimeric transcripts in ependymal tumors

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