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Multi-layered molecular profiling informs the diagnosis and targeted therapy of desmoplastic small round cell tumor

Desmoplastic small round cell tumor (DSRCT) is an ultra-rare sarcoma with limited treatment options. Here, we show that comprehensive molecular profiling informs diagnosis and individualized therapy in this disease. We report the results of whole-genome/exome, transcriptome, and DNA methylome analys...

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Autori principali: Renner, Marcus (Autore) , Oleś, Małgorzata (Autore) , Paramasivam, Nagarajan (Autore) , Heilig, Christoph E. (Autore) , Schneider, Annika (Autore) , Modugno, Caroline (Autore) , Herremans, Catherine (Autore) , Hüllein, Jennifer (Autore) , Hutter, Barbara (Autore) , Erkut, Cihan (Autore) , Mock, Andreas (Autore) , Krieghoff-Henning, Eva (Autore) , Jensen, Cecilia B. (Autore) , Sakhteman, Amirhossein (Autore) , The, Matthew (Autore) , Prinz, Tony (Autore) , Lajer, Panna (Autore) , Baude-Müller, Annika (Autore) , Beck, Katja (Autore) , Beuthien-Baumann, Bettina (Autore) , Apostolidis, Leonidas (Autore) , Bauer, Sebastian (Autore) , Börries, Melanie (Autore) , Brandts, Christian Hubertus (Autore) , Rieke, Damian (Autore) , Kindler, Thomas (Autore) , Klauschen, Frederick (Autore) , Schulze-Osthoff, Klaus (Autore) , Schlenk, Richard Friedrich (Autore) , Berchem, Guy (Autore) , Allgäuer, Michael (Autore) , Mechtersheimer, Gunhild (Autore) , Stenzinger, Albrecht (Autore) , Lipka, Daniel (Autore) , Schlesner, Matthias (Autore) , Kuster, Bernhard (Autore) , Jahn, Arne (Autore) , Schröck, Evelin (Autore) , Heining, Christoph (Autore) , Teleanu, Maria-Veronica (Autore) , Horak, Peter (Autore) , Kreutzfeldt, Simon (Autore) , Hübschmann, Daniel (Autore) , Hartmann, Wolfgang (Autore) , Glimm, Hanno (Autore) , Fröhling, Stefan (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 09 April 2026
In: Nature Communications
Year: 2026, Volume: 17, Pages: 1-17
ISSN:2041-1723
DOI:10.1038/s41467-026-71636-0
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-026-71636-0
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-026-71636-0
Testo
Note sull'autore:Marcus Renner, Małgorzata Oleś, Nagarajan Paramasivam, Christoph E. Heilig, Annika Schneider, Caroline Modugno, Catherine Herremans, Jennifer Hüllein, Barbara Hutter, Cihan Erkut, Andreas Mock, Eva Krieghoff-Henning, Cecilia B. Jensen, Amirhossein Sakhteman, Matthew The, Tony Prinz, Panna Lajer, Annika Baude-Müller, Katja Beck, Bettina Beuthien-Baumann, Leonidas Apostolidis, Sebastian Bauer, Melanie Boerries, Christian H. Brandts, Damian T. Rieke, Thomas Kindler, Frederick Klauschen, Klaus Schulze-Osthoff, Richard F. Schlenk, Guy Berchem, Michael Allgäuer, Gunhild Mechtersheimer, Albrecht Stenzinger, Daniel B. Lipka, Matthias Schlesner, Bernhard Kuster, Arne Jahn, Evelin Schröck, Christoph Heining, Maria-Veronica Teleanu, Peter Horak, Simon Kreutzfeldt, Daniel Hübschmann, Wolfgang Hartmann, Hanno Glimm & Stefan Fröhling
Descrizione
Riassunto:Desmoplastic small round cell tumor (DSRCT) is an ultra-rare sarcoma with limited treatment options. Here, we show that comprehensive molecular profiling informs diagnosis and individualized therapy in this disease. We report the results of whole-genome/exome, transcriptome, and DNA methylome analyses performed in 30 refractory DSRCT patients, complemented by (phospho)proteomic profiling in nine, within a nationwide precision oncology program. In eight patients (27%), DSRCT was diagnosed only after molecular profiling. Although DSRCTs have “quiet” genomes, 28 patients (93%) received 107 molecular-based management recommendations, including assessment of clinical trial eligibility in 17 (57%). Most recommendations are informed by overexpression of tyrosine kinases, SSTR3/5, and CLDN6, detected in 45%, 33%, and 20% of cases, respectively. Thirteen patients (46%) received recommended therapies, yielding disease control in eight (62%), including three long-lasting responses to pazopanib and trastuzumab deruxtecan, the latter administered based on ERBB2 overexpression in the absence of aberrant ERBB2 kinase activation. These findings demonstrate that multi-omics profiling provides clinically actionable insights for DSRCT management.
Descrizione del documento:Gesehen am 08.07.2026
Descrizione fisica:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-026-71636-0

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