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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 (eg, TRK inhibitors in NTRK fusion‐positive tumors). Using targeted next‐generation sequencing, we prospectively analyzed 205 primary brain tumors 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 in‐silico 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 tumor development. ETV1 is a member of the ETS family of transcription factors, already known oncogenic drivers in Ewing sarcoma, prostate cancer and gastrointestinal stromal tumors, but not in gliomas. Its overexpression contributes to tumor growth and more aggressive tumor behavior. PTPRZ1 is already considered to be a tumor 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.

Purpose: To evaluate efficiency of recently developed genotyping microarray, the ABCR400-chip, in combination with the denaturing high performance liquid chromatography (DHPLC) method sequencing to search for known ABCA4 mutations and to associate the findings with phenotype. Methods: 36 Slovenian patients with phenotype of STGD1 were analysed for a population-specific survey on the sequence variations in the ABCA4 gene. In the first step we used the ABCR400 microarray to identify the known mutations. Patients with one or no mutation on ABCR400 microarray were subsequently screened by DHPLC and sequencing. Phenotype was assessed by autofluorescence imaging, psychophysical methods and electrophysiology. Results: By ABCR400 microarray, 25 potential disease-associated alleles were identified resulting in a detection rate of 69.4%. With DHPLC, additional 8 mutations were found: four were novel ABCA4 mutations (two frameshift mutations 5977delT, 5716insG and two missense P597S and P640S). Three novel complex alleles were also identified. Mutation in both alleles were found in 9 patients, and in one allele in 14 cases. In the remaining 3 patients no mutations were found. Different phenotypes were characterised by different patterns of autofluorescence imaging. Electrophysiology,in general, showed normal flash ERG with abnormal PERG and multifocal ERG. Conclusions: Combined approach using ABCR400-chip and DHPLC/sequencing was efficient in detecting over 90% of potential disease-causing mutations in Slovenian Stargardt patients, 4 of which were novel and show distinct genotype/phenotype patterns.