Martine Fohlen1, Ines Harzallah2, Marc Polivka3, Fabienne Giuliano4, Linda Pons5, Nathalie Streichenberger6,7, Georg Dorfmüller8, Renaud Touraine2. 1. Service de neurochirurgie pediatrique, Foundation Rothschild Hospital, Paris, France. fohlen.martine@gmail.com. 2. Service de Génétique Clinique, Chromosomique et Moléculaire, Centre de Compétence des Epilepsies rares (CReER), CHU-Hôpital Nord, Saint Etienne, France. 3. Service d'anatomie et cytologie pathologiques, Hôpital Lariboisière, Paris, France. 4. Service de génétique, Centre Hospitalier Universitaire, Nice, France. 5. Service de Génétique, Centre de Référence des Épilepsies Rares (CReER), Hôpital Femme Mère Enfant, Bron, France. 6. Centre de Pathologie et Neuropathologie Est, Hospices Civils de Lyon; Université Claude Bernard Lyon1, Lyon, France. 7. Institut NeuroMyogène, CNRS UMR 5310-INSERM U1217, Villeurbanne, France. 8. Service de neurochirurgie pediatrique, Foundation Rothschild Hospital, Paris, France.
Abstract
PURPOSE: Subependymal giant-cell astrocytomas (SEGAs) are low grade intraventricular tumors typically found in patients with tuberous sclerosis complex (TSC). The occurrence of SEGA in non TSC patients is very rare and from a genetic point of view these so-called solitary SEGA are thought to result either from somatic mutations in one of the TSC genes (TSC1 or TSC2) limited to the tumor, or be part of a "forme fruste" of TSC with somatic mosaicism. We report on three new cases of solitary SEGA with germline and somatic mutation analysis. METHODS: We retrospectively analyzed TSC genes in three patients with a solitary SEGA using next-generation sequencing technique. RESULTS: In the three patients, a somatic mutation of TSC1 or TSC2 was found only in the tumor cells: one patient had a TSC1 heterozygote mutation, involving the natural acceptor splicing site of intron 15 (c.1998-1G > A (p.?). Two patients had a TSC2 mutation located in the canonical splicing donor site of intron 5 (c.599 + 1G > A) in 70% of the alleles in one patient and in exon 9: c.949_955dup7 (p.V319DfxX21) in 25 of the alleles in the second patient. No other TSC mutations were found in patient's blood or tumor and those identified mutations were absent in blood DNA from parents and siblings. CONCLUSION: We therefore conclude that solitary SEGA can occur with a TSC1 or TSC2 mutation limited to the tumor in patients without TSC.
PURPOSE: Subependymal giant-cell astrocytomas (SEGAs) are low grade intraventricular tumors typically found in patients with tuberous sclerosis complex (TSC). The occurrence of SEGA in non TSC patients is very rare and from a genetic point of view these so-called solitary SEGA are thought to result either from somatic mutations in one of the TSC genes (TSC1 or TSC2) limited to the tumor, or be part of a "forme fruste" of TSC with somatic mosaicism. We report on three new cases of solitary SEGA with germline and somatic mutation analysis. METHODS: We retrospectively analyzed TSC genes in three patients with a solitary SEGA using next-generation sequencing technique. RESULTS: In the three patients, a somatic mutation of TSC1 or TSC2 was found only in the tumor cells: one patient had a TSC1 heterozygote mutation, involving the natural acceptor splicing site of intron 15 (c.1998-1G > A (p.?). Two patients had a TSC2 mutation located in the canonical splicing donor site of intron 5 (c.599 + 1G > A) in 70% of the alleles in one patient and in exon 9: c.949_955dup7 (p.V319DfxX21) in 25 of the alleles in the second patient. No other TSC mutations were found in patient's blood or tumor and those identified mutations were absent in blood DNA from parents and siblings. CONCLUSION: We therefore conclude that solitary SEGA can occur with a TSC1 or TSC2 mutation limited to the tumor in patients without TSC.
Authors: N Kashiwagi; W Yoshihara; N Shimada; H Tanaka; N Fujita; N Hirabuki; Y Watanabe; H Nakamura Journal: Eur J Radiol Date: 2000-01 Impact factor: 3.528
Authors: S Verhoef; L Bakker; A M Tempelaars; A L Hesseling-Janssen; T Mazurczak; S Jozwiak; A Fois; G Bartalini; B A Zonnenberg; A J van Essen; D Lindhout; D J Halley; A M van den Ouweland Journal: Am J Hum Genet Date: 1999-06 Impact factor: 11.025
Authors: John C Kingswood; Guillaume B d'Augères; Elena Belousova; José C Ferreira; Tom Carter; Ramon Castellana; Vincent Cottin; Paolo Curatolo; Maria Dahlin; Petrus J de Vries; Martha Feucht; Carla Fladrowski; Gabriella Gislimberti; Christoph Hertzberg; Sergiusz Jozwiak; John A Lawson; Alfons Macaya; Rima Nabbout; Finbar O'Callaghan; Mirjana P Benedik; Jiong Qin; Ruben Marques; Valentin Sander; Matthias Sauter; Yukitoshi Takahashi; Renaud Touraine; Sotiris Youroukos; Bernard Zonnenberg; Anna C Jansen Journal: Orphanet J Rare Dis Date: 2017-01-05 Impact factor: 4.123