title: Absence of telomerase reverse transcriptase promoter mutations in neuroblastoma.
abstract: Maintenance of telomere length is a critical hallmark of malignant transformation. While silenced in somatic cells, telomerase reverse transcriptase (TERT), the catalytic subunit of telomerase, is frequently overexpressed in malignant cells thereby maintaining their telomere length. Specific point mutations in theTERTpromoter region have recently been identified in melanoma and other tumor entities resulting in high TERT expression. Neuroblastoma is the most common extracranial tumor of childhood, arising from neural-crest progenitor cells. TERT overexpression has been observed in the majority of neuroblastoma. Taking into consideration thatTERTpromoter mutations are frequently described in neural-crest-derived tumors such as melanoma, as well as a variety of other neuronal tumors, the present study analyzed the frequency ofTERTpromoter mutations in primary neuroblastoma and neuroblastoma cell lines. In 131 neuroblastoma primary tumors representing the whole spectrum of neuroblastoma, noTERTpromoter mutations were detected. However, in 3 out of 19 neuroblastoma cell lines the previously described C228TTERTpromoter mutation was present. In conclusion, theTERTpromoter mutations are not a frequent mechanism of TERT overexpression in neuroblastoma.
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, D-45122 Essen, Germany ; German Consortium for Translational Cancer Research (DKTK), Partner Site Essen/Duesseldorf, D-45122 Essen, Germany ; German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Lindner
authors.affiliation: Institute of Pharmacogenetics, University Hospital Essen, D-45147 Essen, Germany.
authors.forename: Hagen S
authors.initials: HS
authors.lastname: Bachmann
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, D-45122 Essen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Odersky
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, D-45122 Essen, Germany ; German Consortium for Translational Cancer Research (DKTK), Partner Site Essen/Duesseldorf, D-45122 Essen, Germany ; German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schaefers
authors.affiliation: Institute of Cell Biology (Cancer Research), Faculty of Medicine, University of Duisburg-Essen, D-45122 Essen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, D-50924 Cologne, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hero
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, D-50924 Cologne, Germany ; Center for Molecular Medicine Cologne (CMMC), University of Cologne, D-50931 Cologne, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Fischer
authors.affiliation: Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin Berlin, D-10117 Berlin, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Eggert
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, D-45122 Essen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schramm
authors.affiliation: Department of Pediatric Oncology and Hematology, University Children's Hospital Essen, D-45122 Essen, Germany ; German Consortium for Translational Cancer Research (DKTK), Partner Site Essen/Duesseldorf, D-45122 Essen, Germany ; German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany ; Translational Neuro-Oncology, West German Cancer Center (WTZ), University Hospital Essen, D-45147 Essen, Germany ; Centre for Medical Biotechnology, University Duisburg-Essen, D-45147 Essen, Germany.
authors.forename: Johannes H
authors.initials: JH
authors.lastname: Schulte
keywords: alternative lengthening of telomeres; neuroblastoma; sequencing; telomerase reverse transcriptase; telomeres