TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals

Chase, Andrew; Ernst, Thomas; Fiebig, Andreas; Collins, Andrew; Grand, Francis; Erben, Philipp; Reiter, Andreas; Schreiber, Stefan; Cross, Nicholas C. P.

doi:10.3324/haematol.2009.011536

Cited by 67 publications

(58 citation statements)

References 28 publications

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“…Exon RPKM for the TCGA data was calculated using script coverageBed in package BEDTools-Version-2.16.2 [49]. The following conditions were met by the fusion transcripts in the curated set: At least one of the breakpoints was a known exon boundary.At least one of the ratios of fusion spanning reads vs. corresponding wild-type exon-exon spanning reads was greater than 2.Number of fusion spanning reads ≥ 100 or outlier z-score value ≥ 5.If only present in potential_fusion.txt then outlier z-score value ≥ 10.Fusion sequence maintains the 5′ → 3′ direction.Not identified in normal tissues (TFG → GPR128 [50]).…”

Section: Methodsmentioning

confidence: 99%

Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data

et al. 2013

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BackgroundRNA-seq has spurred important gene fusion discoveries in a number of different cancers, including lung, prostate, breast, brain, thyroid and bladder carcinomas. Gene fusion discovery can potentially lead to the development of novel treatments that target the underlying genetic abnormalities.ResultsIn this study, we provide comprehensive view of gene fusion landscape in 185 glioblastoma multiforme patients from two independent cohorts. Fusions occur in approximately 30-50% of GBM patient samples. In the Ivy Center cohort of 24 patients, 33% of samples harbored fusions that were validated by qPCR and Sanger sequencing. We were able to identify high-confidence gene fusions from RNA-seq data in 53% of the samples in a TCGA cohort of 161 patients. We identified 13 cases (8%) with fusions retaining a tyrosine kinase domain in the TCGA cohort and one case in the Ivy Center cohort. Ours is the first study to describe recurrent fusions involving non-coding genes. Genomic locations 7p11 and 12q14-15 harbor majority of the fusions. Fusions on 7p11 are formed in focally amplified EGFR locus whereas 12q14-15 fusions are formed by complex genomic rearrangements. All the fusions detected in this study can be further visualized and analyzed using our website: http://ivygap.swedish.org/fusions.ConclusionsOur study highlights the prevalence of gene fusions as one of the major genomic abnormalities in GBM. The majority of the fusions are private fusions, and a minority of these recur with low frequency. A small subset of patients with fusions of receptor tyrosine kinases can benefit from existing FDA approved drugs and drugs available in various clinical trials. Due to the low frequency and rarity of clinically relevant fusions, RNA-seq of GBM patient samples will be a vital tool for the identification of patient-specific fusions that can drive personalized therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-14-818) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data

et al. 2013

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“…TFG was subsequently found as an oncogenic fusion gene in various cancers, including anaplastic large cell lymphoma [6], myxoid chondrosarcoma [7], and atypical myeloproliferative neoplasms [3]. Recently, the gene product, TFG, was implicated in regulating cargo export at the endoplasmic reticulum [23].…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Mapping of TRK-Fused Gene Products in the Rat Brainstem

Takeuchi

Masuda

Maebayashi

et al. 2012

Acta Histochem. Cytochem

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The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It was since reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. As shown in the accompanying paper, we produced an antibody to rat TFG and used it to localize TFG to selected neurons in specific regions. In the present study, we mapped the TFG-positive neurons in the brainstem, cerebellum, and spinal cord of rats. In the brainstem, neurons intensely positive for TFG were distributed in the raphe nuclei, the gigantocellular reticular nucleus, the reticulotegmental nucleus of the pons, and some cranial nerve nuclei such as the trigeminal nuclei, the vestibulocochlear nuclei, and the dorsal motor nucleus of the vagus. Purkinje cells in the cerebellum and motor neurons in the spinal anterior horn were also positive for TFG. These results provide fundamental data for studying the functions of TFG in the brain.

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“…As reported elsewhere, we did find an unusual constitutional polymorphic TFG-GPR128 fusion using our targeted arrays but this was not associated with any obvious phenotype. 44 Since our approach was hypothesis-driven and focused on selected genes we only covered less than 2% of human genes on our targeted arrays and thus other important abnormalities may have been missed. Human genome-wide array CGH or single nucleotide polymorphism array analysis are useful tools for finding alterations that can point to novel candidate genes and pathways and new abnormalities have been detected using these approaches.…”

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Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms

Ernst¹,

Chase²,

Zoi³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundAberrant activation of tyrosine kinases, caused by either mutation or gene fusion, is of major importance for the development of many hematologic malignancies, particularly myeloproliferative neoplasms. We hypothesized that hitherto unrecognized, cytogenetically cryptic tyrosine kinase fusions may be common in non-classical or atypical myeloproliferative neoplasms and related myelodysplastic/myeloproliferative neoplasms. Design and MethodsTo detect genomic copy number changes associated with such fusions, we performed a systematic search in 68 patients using custom designed, targeted, high-resolution array comparative genomic hybridization. Arrays contained 44,000 oligonucleotide probes that targeted 500 genes including all 90 tyrosine kinases plus downstream tyrosine kinase signaling components, other translocation targets, transcription factors, and other factors known to be important for myelopoiesis. ResultsNo abnormalities involving tyrosine kinases were detected; however, nine cytogenetically cryptic copy number imbalances were detected in seven patients, including hemizygous deletions of RUNX1 or CEBPA in two cases with atypical chronic myeloid leukemia. Mutation analysis of the remaining alleles revealed non-mutated RUNX1 and a frameshift insertion within CEBPA. A further mutation screen of 187 patients with myelodysplastic/myeloproliferative neoplasms identified RUNX1 mutations in 27 (14%) and CEBPA mutations in seven (4%) patients. Analysis of other transcription factors known to be frequently mutated in acute myeloid leukemia revealed NPM1 mutations in six (3%) and WT1 mutations in two (1%) patients with myelodysplastic/myeloproliferative neoplasms. Univariate analysis indicated that patients with mutations had a shorter overall survival (28 versus 44 months, P=0.019) compared with patients without mutations, with the prognosis for cases with CEBPA, NPM1 or WT1 mutations being particularly poor. ConclusionsWe conclude that mutations of transcription and other nuclear factors are frequent in myelodysplastic/myeloproliferative neoplasms and are generally mutually exclusive. CEBPA, NPM1 or WT1 mutations may be associated with a poor prognosis, an observation that will need to be confirmed by detailed prospective studies. Haematologica 2010;95(9):1473-1480. doi:10.3324/haematol.2010 This is an open-access paper. Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms

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TFG, a target of chromosome translocations in lymphoma and soft tissue tumors, fuses to GPR128 in healthy individuals

Cited by 67 publications

References 28 publications

Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data

Exploration of the gene fusion landscape of glioblastoma using transcriptome sequencing and copy number data

Immunohistochemical Mapping of TRK-Fused Gene Products in the Rat Brainstem

Transcription factor mutations in myelodysplastic/myeloproliferative neoplasms

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