Ackermann, Sandra ORCID: 0000-0002-5869-7344, Cartolano, Maria, Hero, Barbara, Welte, Anne, Kahlert, Yvonne, Roderwieser, Andrea, Bartenhagen, Christoph, Walter, Esther, Gecht, Judith, Kerschke, Laura, Volland, Ruth, Menon, Roopika, Heuckmann, Johannes M., Gartlgruber, Moritz, Hartlieb, Sabine ORCID: 0000-0003-3746-7010, Henrich, Kai-Oliver, Okonechnikov, Konstantin, Altmueller, Janine, Nuernberg, Peter, Lefever, Steve, de Wilde, Bram, Sand, Frederik, Ikram, Fakhera, Rosswog, Carolina, Fischer, Janina, Theissen, Jessica, Hertwig, Falk ORCID: 0000-0003-4784-6516, Singhi, Aatur D., Simon, Thorsten, Vogel, Wenzel, Perner, Sven, Krug, Barbara, Schmidt, Matthias, Rahmann, Sven, Achter, Viktor, Lang, Ulrich, Vokuhl, Christian, Ortmann, Monika, Buettner, Reinhard, Eggert, Angelika, Speleman, Frank, O'Sullivan, Roderick J., Thomas, Roman K., Berthold, Frank, Vandesompele, Jo, Schramm, Alexander, Westermann, Frank, Schulte, Johannes H., Peifer, Martin and Fischer, Matthias (2018). A mechanistic classification of clinical phenotypes in neuroblastoma. Science, 362 (6419). S. 1165 - 1205. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

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Abstract

Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Spontaneous tumor regression occurred both in the presence and absence of these mutations in patients with telomere maintenance-negative tumors. On the basis of these data, we propose a mechanistic classification of neuroblastoma that may benefit the clinical management of patients.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ackermann, SandraUNSPECIFIEDorcid.org/0000-0002-5869-7344UNSPECIFIED
Cartolano, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hero, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Welte, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kahlert, YvonneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roderwieser, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartenhagen, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walter, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gecht, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerschke, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volland, RuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Menon, RoopikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heuckmann, Johannes M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gartlgruber, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartlieb, SabineUNSPECIFIEDorcid.org/0000-0003-3746-7010UNSPECIFIED
Henrich, Kai-OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Okonechnikov, KonstantinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lefever, SteveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Wilde, BramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sand, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ikram, FakheraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosswog, CarolinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, JaninaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Theissen, JessicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hertwig, FalkUNSPECIFIEDorcid.org/0000-0003-4784-6516UNSPECIFIED
Singhi, Aatur D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogel, WenzelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perner, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krug, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahmann, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Achter, ViktorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vokuhl, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ortmann, MonikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eggert, AngelikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Speleman, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
O'Sullivan, Roderick J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berthold, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vandesompele, JoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schramm, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westermann, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, Johannes H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peifer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fischer, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-162358
DOI: 10.1126/science.aat6768
Journal or Publication Title: Science
Volume: 362
Number: 6419
Page Range: S. 1165 - 1205
Date: 2018
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1095-9203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TELOMERASE ACTIVITY; RNA-SEQ; EXPRESSION; MUTATIONS; FREQUENT; MYCN; REARRANGEMENTS; INHIBITION; ACTIVATION; TUMORSMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16235

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