Marcus Renner, M Oleś, Nagarajan Paramasivam, Christoph E Heilig, Annika Schneider, Caroline Modugno, Catherine Herremans, J Hüllein, Barbara Hutter, Cihan Erkut, Andreas Mock, Eva Krieghoff-Henning, Cecilia B Jensen, Amirhossein Sakhteman, Matthew The, Tony Prinz, Panna Lajer, A Baude-Müller, Katja Beck, Bettina Beuthien-Baumann, Leonidas Apostolidis, Sebastian Bauer, Melanie Boerries, Christian H Brandts, D T Rieke, Thomas Kindler, Frederick Klauschen, Klaus Schulze-Osthoff, Richard F Schlenk, Guy Berchem, M Allgäuer, Gunhild Mechtersheimer, A Stenzinger, Daniel B Lipka, Matthias Schlesner, Bernhard Kuster, Arne Jahn, Evelin Schröck, C Heining, M-V Teleanu, P Horak, Simon Kreutzfeldt, D Hübschmann, Wolfgang Hartmann, Hanno Glimm, Stefan Fröhling
Multi-layered molecular profiling informs the diagnosis and targeted therapy of desmoplastic small round cell tumor.
Nat Commun, 17(1) Art. No. 3397 (2026)
Open Access PubMed Source
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.
@article{Renner9203,
author={Marcus Renner, M Oleś, Nagarajan Paramasivam, Christoph E Heilig, Annika Schneider, Caroline Modugno, Catherine Herremans, J Hüllein, Barbara Hutter, Cihan Erkut, Andreas Mock, Eva Krieghoff-Henning, Cecilia B Jensen, Amirhossein Sakhteman, Matthew The, Tony Prinz, Panna Lajer, A Baude-Müller, Katja Beck, Bettina Beuthien-Baumann, Leonidas Apostolidis, Sebastian Bauer, Melanie Boerries, Christian H Brandts, D T Rieke, Thomas Kindler, Frederick Klauschen, Klaus Schulze-Osthoff, Richard F Schlenk, Guy Berchem, M Allgäuer, Gunhild Mechtersheimer, A Stenzinger, Daniel B Lipka, Matthias Schlesner, Bernhard Kuster, Arne Jahn, Evelin Schröck, C Heining, M-V Teleanu, P Horak, Simon Kreutzfeldt, D Hübschmann, Wolfgang Hartmann, Hanno Glimm, Stefan Fröhling},
title={Multi-layered molecular profiling informs the diagnosis and targeted therapy of desmoplastic small round cell tumor.},
journal ={Nature communications},
volume={17},
issue ={1},
pages={null--null},
year=2026
}