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A novel PTPRZ1-ETV1 fusion in gliomasMatjašič, Alenka, biologija, 1986- ...The aggressive nature of malignant gliomas and their genetic and clinical heterogeneity present a major challenge in their diagnosis and treatment. Development of targeted therapy brought attention ... on detecting novel gene fusions, since they represent promising therapeutic targets (e.g. TRK inhibitors in NTRK fusion-positive tumours). Using targeted next-generation sequencing, we prospectively analysed 205 primary brain tumours and detected a novel PTPRZ1-ETV1 fusion transcript in 11 of 191 (5.8%) gliomas, including nine glioblastomas, one anaplastic oligodendroglioma and one pilocytic astrocytoma. PTPRZ1-ETV1 fusion was confirmed by RT-PCR followed by Sanger sequencing, and insilico analysis predicted a potential driver role. The newly detected fusion consists of the PTPRZ1 promoter in frame with the highly conserved DNA-binding domain of ETV1 transcription factor. The ETV1 and PTPRZ1 genes are known oncogenes, involved in processes of tumour development. ETV1 is a member of the ETS family of transcription factors, already known oncogenic drivers in Ewing sarcoma, prostate cancer and gastrointestinal stromal tumours, but not in gliomas. Its overexpression contributes to tumour growth and more aggressive tumour behaviour. PTPRZ1 is already considered to be a tumour growth promoting oncogene in gliomas. In 8-16% of gliomas, PTPRZ1 is fused to the MET oncogene, resulting in a PTPRZ1-MET fusion, which is associated with poorer prognosis but is also a positive predictive biomarker for treatment with kinase inhibitors. In view of the oncogenic role that the two fusion partners, PTPRZ1 and ETV1, exhibit in other malignancies, PTPRZ1-ETV1 fusion might present a novel potential therapeutic target in gliomas. Although histopathological examination of PTPRZ1-ETV1 fusion-positive gliomas did not reveal any specific or unique pathological features, and the follow-up period was too short to assess prognostic value of the fusion, careful monitoring of patients and their response to therapy might provide additional insights into the prognostic and predictive value of this novel fusion.Source: Brain pathology. - ISSN 1015-6305 (Vol. 30, iss. 2, Mar. 2020, str. 226-234)Type of material - article, component part ; adult, seriousPublish date - 2020Language - englishCOBISS.SI-ID - 34444761
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Matjašič, Alenka, biologija, 1986- | 35428 |
Zupan, Andrej, 1981- | 28143 |
Boštjančič, Emanuela, 1979 | 25441 |
Pižem, Jože | 26058 |
Popović, Mara | 07090 |
Kolenc, Danijela | 52857 |
Source: Personal bibliographies
and: SICRIS
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