Nozomi Matsumura1, Sumihito Nobusawa2, Junko Ito3, Akiyoshi Kakita3, Hiroyoshi Suzuki4, Yukihiko Fujii5, Masafumi Fukuda6, Masaki Iwasaki7, Nobukazu Nakasato8, Teiji Tominaga9, Atsushi Natsume10, Yoshiki Mikami11, Naoki Shinojima12, Tatsuya Yamazaki2, Yoichi Nakazato13, Junko Hirato14, Hideaki Yokoo2. 1. Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan. nozomim@gunma-u.ac.jp. 2. Department of Human Pathology, Gunma University Graduate School of Medicine, 3-39-22, Showa-machi, Maebashi, Gunma, 371-8511, Japan. 3. Department of Pathology, Brain Research Institute, Niigata University, Niigata, Niigata, Japan. 4. Department of Pathology and Laboratory Medicine, National Hospital Organization Sendai Medical Center, Sendai, Miyagi, Japan. 5. Department of Neurosurgery, Brain Research Institute, Niigata University, Niigata, Niigata, Japan. 6. Department of Neurosurgery, Nishi-Niigata Chuo National Hospital, Niigata, Niigata, Japan. 7. Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. 8. Department of Epileptology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. 9. Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. 10. Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Aichi, Japan. 11. Department of Diagnostic Pathology, Kumamoto University Hospital, Kumamoto, Kumamoto, Japan. 12. Department of Neurosurgery, Kumamoto University Hospital, Kumamoto, Kumamoto, Japan. 13. Department of Pathology, Hidaka Hospital, Takasaki, Gunma, Japan. 14. Department of Diagnostic Pathology, Gunma University Hospital, Maebashi, Gunma, Japan.
Abstract
PURPOSE: Dysembryoplastic neuroepithelial tumors (DNTs) are slow-growing glioneuronal tumors, and their genetic backgrounds are getting unveiled. Recently, fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain (TKD) has been demonstrated by whole-genome sequencing. METHODS AND RESULTS: Here, we analyzed 22 DNTs using multiplex ligation-dependent probe amplification (MLPA) with formalin-fixed paraffin-embedded specimens and found a copy number gain in TKD of FGFR1 (13 cases, 59%), which suggested the presence of FGFR1-ITD. Another 5 DNTs harbored FGFR1 hot spot mutations including a double mutant case, and FGFR1 alterations were detected in 18 DNTs (82%). The BRAF V600E mutation, another important mutation in DNTs, was not observed. CONCLUSIONS: With recent findings of less frequent or absent FGFR1-ITD in pilocytic astrocytomas or rosette-forming glioneuronal tumors, the analysis of FGFR1 aberrations, especially FGFR1-ITD, was suggested to be helpful to discriminate DNTs from their histological mimics.
PURPOSE:Dysembryoplastic neuroepithelial tumors (DNTs) are slow-growing glioneuronal tumors, and their genetic backgrounds are getting unveiled. Recently, fibroblast growth factor receptor 1 internal tandem duplication (FGFR1-ITD) of the tyrosine kinase domain (TKD) has been demonstrated by whole-genome sequencing. METHODS AND RESULTS: Here, we analyzed 22 DNTs using multiplex ligation-dependent probe amplification (MLPA) with formalin-fixed paraffin-embedded specimens and found a copy number gain in TKD of FGFR1 (13 cases, 59%), which suggested the presence of FGFR1-ITD. Another 5 DNTs harbored FGFR1 hot spot mutations including a double mutant case, and FGFR1 alterations were detected in 18 DNTs (82%). The BRAFV600E mutation, another important mutation in DNTs, was not observed. CONCLUSIONS: With recent findings of less frequent or absent FGFR1-ITD in pilocytic astrocytomas or rosette-forming glioneuronal tumors, the analysis of FGFR1 aberrations, especially FGFR1-ITD, was suggested to be helpful to discriminate DNTs from their histological mimics.