title: TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors.
abstract: Whole-genome sequencing detected structural rearrangements of TERT in 17 of 75 high-stage neuroblastomas, with five cases resulting from chromothripsis. Rearrangements were associated with increased TERT expression and targeted regions immediately up- and downstream of TERT, positioning a super-enhancer close to the breakpoints in seven cases. TERT rearrangements (23%), ATRX deletions (11%) and MYCN amplifications (37%) identify three almost non-overlapping groups of high-stage neuroblastoma, each associated with very poor prognosis.
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Valentijn
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Danny A
authors.initials: DA
authors.lastname: Zwijnenburg
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Hasselt
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: van Sluis
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: Volckmann
authors.affiliation: Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
authors.forename: Max M
authors.initials: MM
authors.lastname: van Noesel
authors.affiliation: Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Rani E
authors.initials: RE
authors.lastname: George
authors.affiliation: Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.|Department of Pediatric Oncology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Godelieve A M
authors.initials: GA
authors.lastname: Tytgat
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Molenaar
authors.affiliation: Department of Oncogenomics, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
mesh_terms: D004265:DNA Helicases / Q000235:genetics; D005784:Gene Amplification; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D000075924:X-linked Nuclear Protein
chemical_list: C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C509186:TERT protein, human; D019098:Telomerase; D004265:DNA Helicases; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein